INCREASING THE EFFICIENCY OF PROTEIN PRODUCTION IN DAIRY CATTLE

• Sponsoring Institution: National Institute of Food and Agriculture
• Project Status: COMPLETE
• Funding Source: HATCH
• Reporting Frequency: Annual
• Accession No.: 0150566
• Project Start Date: May 1, 2010
• Project End Date: Apr 30, 2015
• Program Code: [(N/A)]- (N/A)

Recipient Organization
MICHIGAN STATE UNIV
(N/A)
EAST LANSING,MI 48824

Performing Department
Animal Science

Non Technical Summary
The typical cow has a maintenance requirement of about 10 Mcal Net Energy for Lactation (NEL) per day. Each kg of milk takes an additional 0.7 Mcal NEL. Thus, the cow producing 45 kg of milk per day needs four times as much energy as she needs for her maintenance requirement alone. The elite cow producing 90 kg/day needs seven times as much energy as she needs for maintenance. Consequently, the efficiency of using feed energy is much greater for this elite cow than it was for the cow of 100 years ago consuming a diet of mostly forage. With increased productivity also has come the need for fewer cows to produce milk on a per capita basis and increases in net income per cow. However, compared to energetic efficiency, the efficiency of using feed protein to make milk protein has not increased as dramatically, partly because cows are often fed protein in excess. Any consumed N that is not captured in milk or body tissues must be excreted. This N waste is an environmental concern; N losses in manure contribute to water pollution and ammonia emissions from dairy farms. There is increasing pressure from society and governmental agencies to decrease environmental effects of animal farming. Much of the N excreted from a cow is lost as urinary urea, and it is rapidly hydrolyzed to ammonia by urease enzymes in feces or soil. Ammonia is emitted in the barn and during storage, composting, or application of manure. Ammonia emissions from animal agriculture account for ~50% of total ammonia emissions from terrestrial systems, and ammonia is implicated as a cause of haze, acid rain, and eutrophication. Animal agriculture also contributes to N2O, NO, and NO2 emissions, and these compounds have been implicated in global climate change (NRC, 2003). New technologies for manure management will help reduce ammonia emissions, but many of these technologies may be cost-prohibitive for smaller farms. Thus, the long-term solution to decrease ammonia emissions must include improvements in the biological efficiency of protein use. However, the complexities of protein nutrition and limitations in measuring feed N fractions make accurate specifications for feed protein fractions difficult. The economic risk of underfeeding protein is greater than the risk of overfeeding protein, so protein efficiency has not been maximized in the past, nor is it likely to be maximized in the foreseeable future unless we devise new strategies to do so (VandeHaar and St-Pierre, 2006). Increasing the efficiency of converting dietary protein to milk and meat can help us meet this challenge for animal agriculture in the future. This project will focus on two ways to enhance the efficiency of protein use: 1) increasing production per cow per day of life and 2) minimizing feed N intake per unit of milk produced in lactating cows while supporting high production. To increase milk production per day of life, we seek new ways to manage dairy heifers for earlier calving and/or increased milk production. To minimize feed N intake per unit milk production, we will find new ways to match dietary protein with animal genotype.

Animal Health Component

(N/A)

Research Effort Categories

Basic

(N/A)

Applied

(N/A)

Developmental

(N/A)

Classification

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
302	3410	1010	80%
302	3499	1010	10%
315	3410	1010	10%

Knowledge Area
302 - Nutrient Utilization in Animals; 315 - Animal Welfare/Well-Being and Protection;

Subject Of Investigation
3499 - Dairy cattle, general/other; 3410 - Dairy cattle, live animal;

Field Of Science
1010 - Nutrition and metabolism;

Keywords

dairy cattle

milk production

efficiency

protein

nutrition

heifer

growth

Goals / Objectives
The overall goal of this project is to increase the efficiency of protein production and the quality of meat and milk in ruminants primarily through nutritional methods. More specifically, the objectives are to: 1. Discover methods to manage dairy heifers for efficient and cost-effective body and mammary growth. a. Determine how diet alters immune function of calves. b. Determine how diet alters the timing of the switch to slower mammary growth around puberty. c. Identify key metabolic regulators that mediate effects of nutrition on mammary development. 2. Discover methods to achieve high milk production with less protein in dairy cow diets. a. Identify key signals that control efficiency of converting dietary protein to milk protein. b. Identify cows that can produce copious amounts of milk with less dietary protein. c. Identify genetic markers associated with improved protein efficiency.

Project Methods
We plan to identify events in reproductive development that are associated with the truncation of allometric mammary growth and determine how nutrition alters their timing. We will feed heifers starting at 100 kg BW for 1200 or 600 g/d of BW gain. Blood will be sampled frequently, and heifers will be killed at 100 kg intervals. We will examine ovarian activity and reproductive hormones before slaughter. The time to isometric mammary growth will be compared with the time to first LH pulses and first detected increases in serum progesterone. We also plan to identify novel genes that might explain the comparative responses of mammary parenchymal and other body tissues to high energy diets before and after puberty. We also will work with mammary epithelial cells to understand the controls of proliferation, differentiation, and metabolism. Finally, we will examine effects of nutrition of milk-fed calves on growth and long-term efficiency. This includes examining effects of omega-3 fatty acids on immune function and subsequent health. Newborn calves (n=48) will be purchased, housed individually, and fed a standard milk replacer on day of arrival. New calves will be randomly assigned to treatments and fed for 4 wk. All milk replacers will be isocaloric and isoFA. Blood samples will be collected to examine expression of white blood cell genes indicative of immunocompetence with and without stimulation by endotoxin. Health, growth, and food intake will be monitored. These studies will determine methods to cost-effectively and efficiently raise heifers to become high-producing cows. We also are determining effects of low and high protein diets on the metabolic genomics of lactating dairy cows. Expression of genes associated with protein catabolism, ureagenesis, and gluconeogenesis in liver and milk protein synthesis and amino acid transport in mammary gland will be compared to milk protein yield and milk urea nitrogen data to select possible candidate genes that might be involved in regulating the efficiency of protein use. We will analyze data from Michigan Dairy Herd Improvement records using novel statistical methodology to model variability in milk production as a function of various management factors. Cow level variables to be modeled include individual indicators of productive performance, milk urea nitrogen (MUN; an indicator of wasted N), and genetic merit. These data will be paired to correlate yield of milk and milk protein on herd test day to MUN and to predicted genetic merit (if known) based on sire and dam. Data will be categorized according to average herd test day MUN as an indicator of dietary protein sufficiency. Finally, we hope to determine the genetic correlations for efficiency of N use in at least 1000 cows to determine if some cows can produce copious quantities of milk with diet containing less protein and to begin determining if genomic variability might explain the genetic component of N efficiency.

Progress 05/01/10 to 04/30/15

Outputs
Target Audience:Target audience includes other researchers as well as extension specialists, farmers, and farm consultants, graduate and, undergraduate students, and the general populace. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Two graduate and six undergraduate students received training in dairy cattle nutrition and in research. How have the results been disseminated to communities of interest?Research publications, conference presentations and proceedings, and scientific presentations. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? This project is related to MICL08463, from which nearly all of my laboratory's current funding was obtained, and to projects by Dr. A.L. Lock, and work on partioning of nutrients in late lactation. These results are reported in detail in CRIS reports for those projects. In brief, we found and reported that residual feed intake as a heritable trait and that initial genomic relationships were great enough to expect that genomic breeding values for RFI could be useful. We found that RFI was repeatable across diets and lactations. We confirmed that diets with less starch and more digestible fiber could help to partition feed nutrients toward milk production in late lactation cows and prevent excess gain of body fat.

Publications

• Type: Journal Articles Status: Published Year Published: 2015 Citation: Contreras-Govea, F. E., V. E. Cabrera, L. E. Armentano, R. D. Shaver, P. M. Crump, D. Beede, and M. VandeHaar. 2015. Constraints for nutritional grouping in Wisconsin and Michigan dairy farms. J. Dairy Sci. 98:1336-1344.
• Type: Journal Articles Status: Published Year Published: 2015 Citation: Hardie,L., L. E. Armentano, R. D. Shaver, M. J. VandeHaar, D. M. Spurlock, C. Yao, S. J. Bertics, F. E. Contreras-Govea, and K. A. Weigel. 2015 Considerations when combining data from multiple nutrition experiments to estimate genetic parameters for feed efficiency. J. Dairy Sci. 98:2727-2737.
• Type: Journal Articles Status: Published Year Published: 2015 Citation: Potts, S. B., J. P. Boerman, A. L . Lock, M. S. Allen, and M. J. VandeHaar. 2015. Residual feed intake is repeatable for lactating Holstein dairy cows fed high and low starch diets. J Dairy Sci 98:4735-4747.
• Type: Conference Papers and Presentations Status: Awaiting Publication Year Published: 2015 Citation: VandeHaar, M. J., and D. M. Spurlock. 2015. Using residual feed intake as a tool to improve dairy feed efficiency. J Animal Sci. (in press; invited oral presentation at Midwest ADSA meetings, March 2015)
• Type: Conference Papers and Presentations Status: Published Year Published: 2014 Citation: VandeHaar, M.J., Y. Lu, D. M. Spurlock, L. E. Armentano, K. A. Weigel, R. F. Veerkamp, M. Coffey, Y. de Haas, C. R. Staples, E. E. Connor, M. D. Hanigan, R. J. Tempelman. 2014. Phenotypic and genetic correlations among milk energy output, body weight, and feed intake, and their effects on feed efficiency in lactating dairy cattle. Abstract 157 at the Fed Animal Sci Soc. J Dairy Sci 97(E-Suppl)
• Type: Journal Articles Status: Published Year Published: 2015 Citation: Tempelman, R. J., D. M. Spurlock, M. Coffey, R. F. Veerkamp, L. E. Armentano, K. A. Weigel, Y. de Haas, C. R. Staples, Y. Lu, and M. J. VandeHaar. 2015. Heterogeneity in genetic and non-genetic variation and energy sink relationships for residual feed intake across research stations and countries. J. Dairy Sci. 98:2013-2026.
• Type: Conference Papers and Presentations Status: Published Year Published: 2014 Citation: Burczynski, S.E., J. P. Boerman, A. L. Lock, M. S. Allen, and M. J. VandeHaar. 2014. Relationship Between digestibility and residual feed intake in lactating Holstein cows fed high and low starch diets. Abstract 346 at the Fed Animal Sci Soc. J Dairy Sci 97(E-Suppl)
• Type: Journal Articles Status: Published Year Published: 2015 Citation: Yao, C., L. E. Armentano, M. J. VandeHaar, and K. A. Weigel. 2015. Short communication: Use of single nucleotide polymorphism genotypes and health history to predict future phenotypes for milk production, dry matter intake, body weight, and residual feed intake in dairy cattle. J. Dairy Sci. 98:2027-2032.
• Type: Journal Articles Status: Published Year Published: 2015 Citation: Boerman, J. P., S.B. Potts, M.J. VandeHaar, M.S. Allen, and A.L. Lock. 2015. Milk production responses to a change in dietary starch concentration vary by production level in dairy cattle. J. Dairy Sci. 98:4698-4706.
• Type: Conference Papers and Presentations Status: Other Year Published: 2014 Citation: Spurlock, D. M., R. J. Tempelman, K. A. Weigel, L. E. Armentano, G. R. Wiggans, R. F. Veerkamp, Y. de Haas, M. P. Coffey, M. D. Hanigan, C. Staples, and M. J. VandeHaar. 2014. Genetic architecture and biological basis of feed efficiency in dairy cattle. Proc. 10th World Congress on Genetics Applied to Livestock Production, August 17-23, Vancouver, BC (Abstr. 287).
• Type: Conference Papers and Presentations Status: Published Year Published: 2014 Citation: Boerman, J.P., S. E. Burczynski, M. J. VandeHaar, and A. L. Lock. 2014. Effects of diets differing in starch, fiber, and fatty acid concentrations on milk production and energy partitioning. Abstract 604 at the Fed Animal Sci Soc. J Dairy Sci 97(E-Suppl)

Progress 10/01/13 to 09/30/14

Outputs
Target Audience: Target audience includes other researchers as well as extension specialists, farmers, and farm consultants, graduate and, undergraduate students, and the general populace. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Two MS and ten undergraduate students received training. How have the results been disseminated to communities of interest? Nutrition conferences and publications. What do you plan to do during the next reporting period to accomplish the goals? We are continuing to examine the role of digestibility and other animal factors in determining which animals are most efficient within a cow herd. We will also examine methods to achieve maximum milk production and efficiniency for cows in late lactation.

Impacts
What was accomplished under these goals? This project is related to MICL08463, from which nearly all of my laboratory's current funding was obtained. The heritability ofresidual feed intake (RFI) using data from about 5000 cows in univiersity herds within North America and Europe was determined to be 0.16. We determined if differences in digestibility among cows explained variation in residual feed intake (RFI) in 4 cross-over design experiments. Lactating Holstein cows (n=109; 120±30 DIM; mean ± SD) were fed diets high (HS) or low (LS) in starch. LS diets were ~40% NDF and ~14% starch; HS diets were ~26% NDF and ~30% starch. Each experiment consisted of two 28-d treatment periods, with digestibility measured during the last 5 d. Individual DMI and milk yield were recorded daily, BW was measured 3-5 times per wk, and milk components were analyzed 2 d/wk. Individual DMI was regressed on milk energy output, metabolic BW, body energy gain, and fixed effects of parity, experiment, cohort nested within experiment, and diet nested within cohort and experiment, with the residual being RFI. High RFI cows eat more than expected and deemed less efficient. RFI was correlated negatively with digestibility of starch for both HS (r=-0.31; P<0.01) and LS diets (r=-0.23; P=0.02), and with digestibilities of DM (r=-0.30; P<0.01) and NDF (r=-0.23; P=0.02) for LS diets but not HS diets (P>0.3). For each cohort, cows were classified as high RFI (HRFI; >0.5 SD), medium RFI (MRFI; ±0.5 SD), and low RFI (LRFI; <-0.5 SD). Digestibility of DM was similar (~66%) among HRFI and LRFI cows for HS diets. For both diets, HRFI cows ate at a higher multiple of maintenance (P<0.05), and feed intake as a multiple of maintenance was positively related to RFI (P<0.01). Although digestibility was different between HRFI and LRFI cows, some of the differences were expected because cows with high RFI eat at a higher multiple of maintenance, which could depress digestibility. Differences in intakeas a multiple of maintenance accounted for most of the differences (84%) in DM digestibility observed among HRFI and LRFI cows for LS diets. Based on these data, we conclude that a cow's digestive ability explains none of the variation in RFI for cows eating high starch diets but 9% of the variation in RFI when cows are fed low starch diets. Because cows with high RFI ate more, it is unlikely that digestibility directly influenced RFI status; however, cows with low RFI ate less, probably because of a superior ability to convert digested energy into net energy, and consequently had the additional energetic advantage of being able to digest their feed more efficiently.

Publications

• Type: Journal Articles Status: Published Year Published: 2014 Citation: Karcher, E.L., T.M. Hill, H.G. Bateman, R.L. Schlotterbeck, N. Vito, L.M. Sordillo, M.J. Vandehaar. 2014. Comparison of supplementation of n-3 fatty acids from fish and flax oil on cytokine gene expression and growth of milk-fed Holstein calves. J Dairy Sci. 97:2329-2337.
• Type: Conference Papers and Presentations Status: Published Year Published: 2014 Citation: VandeHaar MJ 2014 Opportunities for improving feed efficiency. Proc Tri-State Dairy Nutr Conf., Fort Wayne, IN.
• Type: Conference Papers and Presentations Status: Published Year Published: 2014 Citation: VandeHaar MJ 2014 Feeding and breeding for a more efficient cow. Proc West Canada Dairy Seminar, Red Deer, Alberta, Canada
• Type: Conference Papers and Presentations Status: Published Year Published: 2014 Citation: VandeHaar, M.J., Y. Lu, D. M. Spurlock, L. E. Armentano, K. A. Weigel, R. F. Veerkamp, M. Coffey, Y. de Haas, C. R. Staples, E. E. Connor, M. D. Hanigan, R. J. Tempelman. 2014. Phenotypic and genetic correlations among milk energy output, body weight, and feed intake, and their effects on feed efficiency in lactating dairy cattle. Abstract 157 at the Fed Animal Sci Soc. J Dairy Sci 97(E-Suppl)
• Type: Conference Papers and Presentations Status: Published Year Published: 2014 Citation: Burczynski, S.E., J. P. Boerman, A. L. Lock, M. S. Allen, and M. J. VandeHaar. 2014. Relationship Between digestibility and residual feed intake in lactating Holstein cows fed high and low starch diets. Abstract 346 at the Fed Animal Sci Soc. J Dairy Sci 97(E-Suppl)
• Type: Conference Papers and Presentations Status: Published Year Published: 2014 Citation: Boerman, J.P., S. E. Burczynski, M. J. VandeHaar, and A. L. Lock. 2014. Effects of diets differing in starch, fiber, and fatty acid concentrations on milk production and energy partitioning. Abstract 604 at the Fed Animal Sci Soc. J Dairy Sci 97(E-Suppl)

Progress 01/01/13 to 09/30/13

Outputs
Target Audience: Target audience includes other researchers as well as extension specialists, farmers, and farm consultants, graduate and undergraduate students, and the general populace Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Students in a study-abroad program in the Netherlands took pictures to use in developing K-12 teaching programs on feed efficiency. Undergraduate students were mentored in research in feed efficiency, with 12 students directly involved in the work at MSU. In addition, 3 graduate students have been working on the project and learning about the genetics and management of feed efficiency. How have the results been disseminated to communities of interest? Results were disseminated in journal articles, regional or international management conferences with proceedings, presentations at the annual meetings of the Am Dairy Sci Assoc with corresponding journal abstracts, and several extension, university, and project seminars without proceedings. In addition, an ADSA Discover Conference was developed and cochaired by M VandeHaar on the topic of dairy feed efficiency with attendence sold out at >160 partcipants from around the world. VandeHaar gave the keynote presentation. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? This project is related to Project MICL08463, from which nearly all of our lab's current funding was obtained. In the past year, we added phenotypes for nutrient input and output from 2700 new cows to our multi-university database to bring the total to 5300 individual cow phenotypes. The overall heritability from 60 to 90 DIM across all research stations was 0.14 ± 0.03. Hence future genomic selection programs on feed efficiency appear to be promising. We also examined the repeatability of RFI when cows are fed high vs low starch diet on 90 MI cows. As we develop genomic selection tools for efficiency, our goal is to identify animals that are efficient on many different diets. Holstein cows averaging 670 kg of BW, 40 kg of milk/d, and 125 d postpartum at experiment start, were fed diets of high or low starch content in 3 crossover experiments with 4-wk periods. High starch diets were approximately 27% NDF and 30% starch and low starch diets were about 40% NDF and 12 to 16% starch. These differences were achieved mostly by replacing corn grain with soyhulls. High starch diets increased milk energy output by 7%, DMI by 3%, and percentage of gross energy captured as milk and body tissue (GEcap) by 9% (P <0.01) across experiments and parity. The mean absolute difference in RFI between treatments across experiments was 0.9 kg (SD = 0.7). The correlation between RFI when cows were fed the high starch diets and RFI when cows were fed the low starch diets was 0.79 (P<0.01) and was similar within each parity and experiment. The feed efficiency measures of milk/feed, GEcap, and Income over feed cost for individual cows also were repeatable across high and low starch diets (r=0.78, 0.72, and 0.85, respectively). We concluded that RFI is reasonably repeatable for a wide range of dietary starch concentrations so that cows that are most efficient when fed high corn diets are likely also most efficient when fed diets high in non-forage fiber sources. Another goal within Aim 2 was to characterize the genomic architecture of feed efficiency and search for significant SNP relationships. The data from 400 Iowa cows were analyzed in year 2 using a random forest (RF) algorithm. Among the 15 SNPs identified as significant, 7 are located within reported quantitative trait locus intervals for RFI in beef cattle, 6 are associated with annotated genes, and 5 are located in the introns of known genes. In cooperation with Mark Hanigan of Virginia Tech, the Dairy NRC 2001 nutrition model was evaluated using production data from 99 published studies from 1983 through 2011, using 374 diets, of which 305 included milk production data. SAS 9.3 was used to individually write each diet into a spreadsheet containing equations of the NRC model. In our preliminary analyses, we found the error of prediction for AA- and MP-allowable milk exceeds NEL -allowable milk prediction errors. Mean bias associated with NEL -allowable milk was positive (underprediction), whereas MP-allowable milk predictions tended to be negative (overprediction). An ADSA Discover Conference was developed and co-chaired by M VandeHaar on the topic of dairy feed efficiency with attendence sold out at >160 partcipants from around the world.

Publications

• Type: Conference Papers and Presentations Status: Published Year Published: 2013 Citation: Burczynski, S.E., J.S. Liesman, R.J. Tempelman, J.C. Ploetz, M.S. Allen, A.L. Lock, and M.J. VandeHaar. 2013. Residual feed intake is repeatable when high and low starch diets are fed to lactating Holstein dairy cows. J. Dairy Sci. 96(ESuppl.): 397. Abstr 331 at Fed Anim Sci Soc.
• Type: Conference Papers and Presentations Status: Published Year Published: 2013 Citation: Tempelman, R., R. Veerkamp, M. Coffey, D. Spurlock, L. Armentano, K. Weigel, Y. de Haas, C. Staples, M. Hanigan, M. VandeHaar. 2013. Heterogeneity across research stations in genetic variation and energy sink relationships for feed efficiency in lactating dairy cattle. J. Dairy Sci. 96(E-Suppl.):389. Abstr 310 at Fed Anim Sci Soc
• Type: Journal Articles Status: Published Year Published: 2013 Citation: Jacobs, A. A. A., J. S. Liesman, M. J. VandeHaar, J. Dijkstra, A. M. van Vuuren, and J. van Baal. 2013. Effects of short and long-chain fatty acids on expression of lipogenic genes in bovine mammary epithelial cells. Animal 7:1508-1516.
• Type: Journal Articles Status: Published Year Published: 2013 Citation: Yao, C., D. M. Spurlock, K. A. Weigel, L. E. Armentano, C. D. Page, Jr., and M. J. VandeHaar. 2013. Random Forest Approach for Identifying Additive and Epistatic SNPs Associated with Residual feed Intake in Dairy Cattle. J Dairy Sci 96:6716-6729.
• Type: Journal Articles Status: Published Year Published: 2013 Citation: VandeHaar MJ. 2013. What are our Opportunities for Improving Dairy Feed Efficiency? Keynote address at the ADSA Discover Conference #26, Naperville, IL, Sept 23.

Progress 01/01/12 to 12/31/12

Outputs
OUTPUTS: Genomic selection in the dairy industry will enable selection of breeding stock for feed efficiency, a trait which is complex to define. We are developing a database is to quantify relationships among factors that affect dairy feed efficiency. Data from 1600 Holstein cows in the US (university herds in WI, IA, MI, VA, and FL) and another 3000 in Europe are included to date, and additional studies have been initiated so that we eventually collect data on 8000 cows. Currently, we are quantifying phenotypic relationships among and within cows and determining the heritability of feed efficiency. Cows are being genotyped with the 50K SNP platform to characterize genomic relationships for feed efficiency of lactating Holstein cows. Feed efficiency is being examined several ways, but our early focus is on residual feed intake (RFI), a measure of actual versus predicted intake for an individual. We also conducted studies on 56 cows to examine repeatability of feed efficiency and digestibility traits for cows on high corn grain vs high soyhull diets. We are using our database to determine if there is an optimal level of milk production to maximize feed efficiency. On average, as cows eat more as a multiple of maintenance and produce more milk, feed energy is captured more efficiently. However, the marginal increase in efficiency is expected to decrease with increasing productivity, especially with the decrease in digestibility predicted by National Research Council. Events: Results of these studies were reported at the Federation of Animal Science Society meetings. Products: The Spartan Dairy Ration Formulation 3 software continued to be sold as a tool to ensure that scientific findings impact nutritional efficiency on commercial dairy farms. PARTICIPANTS: Partner organizations in studies during the past year include University of Wisconsin at Madison, Iowa State University, Wageningen University (The Netherlands), Virgina Technical University, and the University of Florida. Collaborators at Michigan State University include Drs. Robert Tempelman, Mirian Weber Nielsen, Elizabeth Karcher, David Beede, Michael Allen, and Adam Lock. These studies provided opportunity for training eight undergraduate students. TARGET AUDIENCES: Target audience includes other dairy scientists, consulting nutritionists and veterinarians. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Based on initial results with 840 cows, most of the advantage of higher productivity for gross feed efficiency is obtained once Holstein cows are eating at >4X maintenance (milk yield >40 kg/cow/day). Cows at 5 or 6X maintenance intake were only slightly more efficient, but efficiency varied considerably in these cows. We suggest that once cows are above 3X maintenance on a lifetime basis, further increases in productivity (or decreased body size with same milk output) will return little gain in gross efficiency. Rather direct selection and management for efficiency should be a focus. Our best estimate at predicting DMI accounted for 77% of the variation in observed DMI across this dataset. Accurate measure of body weight gain or loss is necessary to ensure selection is not biased toward cows losing body energy; however, for cows in mid-lactation, body weight change did not have a major impact on our ability to identify efficient cows. In contrast, milk composition was a major contributor in determining feed efficiency, and accurate measures of milk composition are likely critical to successful identification of efficient cows. Selecting cows for RFI (based on milk, body weight, and body weight change) puts no selective pressure on cow size, and when accompanied by continued selection for milk will likely result in heavier cows. Our initial data suggest that a reasonable option would be to assign an RFI penalty of 0.1 kg feed DM per unit of mBW above 140. Careful consideration of all factors affecting feed efficiency, including RFI, maintenance requirements, and production, will be necessary to achieve continued improvement of feed efficiency.

Publications

• VandeHaar, M., D. M. Spurlock, L. Armentano, R. Tempelman, K. Weigel, and R. Veerkamp. 2012. Considerations in using residual feed intake to define feed efficiency in dairy cattle. J. Dairy Sci. 95(suppl.2):268.
• VandeHaar, M., L. Armentano, D. M. Spurlock, J. Patience, and J. Taylor. 2012. Feed efficiency: Basic principles and opportunities for improvement. J. Anim. Sci. 90(suppl.3):398.
• Yao, C., D. M. Spurlock, K. A. Weigel, L. E. Armentano, C. D. Page, and M. J. VandeHaar. 2012. Random forest approach for SNP effects of residual feed intake in dairy cattle. J. Dairy Sci. 95(suppl.2):682-683.
• Block, E., B. Bradford, W. M. Chalupa, I. J. Lean, S. LeBlanc, M. C. Lucy, J. McNamara, J. Morton, A. R. Rabiee, J. E. P. Santos, W. W. Thatcher, M. Van Amburgh, and M. J. VandeHaar. 2012. Integration of experimental designs and analytical approaches to co-ordinate efficiency of global efforts to optimize environmental and genetic effects on reproductive performance of dairy cattle. J. Dairy Sci. 95(suppl.2):685.

Progress 01/01/11 to 12/31/11

Outputs
OUTPUTS: Activities: We conducted and analyzed data from experiments on calf nutrition, the regulation of mammary lipid and protein metabolism, and efficiency of milk production. We finished analysis of an experiment to examine effects of fatty acid supplements on immune function. Blood samples had been collected from calves after feeding milk replacers based on lard and supplemented with 2% lard, 2% fish oil, or 2% flax oil. Quantitative RT-PCR was used to assess the effects of lipopolysaccharide stimulation on expression of key genes associated with immune function. In collaboration with researchers from Wageningen University, The Netherlands, we finished analysis of data from a study to determine the effect of the short-chain fatty acids on expression of lipogenic genes in a bovine mammary epithelial cell line (MAC-T). We also continued analysis of samples to determine the effect of dietary protein on expression of mammary genes. We measured expression of several genes associated with protein transport and metabolism in 36 mammary biopsy samples from 12 cows in mid-lactation fed each of 3 diets with varying concentrations of protein (11, 15, and 19% protein with added CP mostly from expeller soybean meal) for 11-day periods in a Latin square design. Finally, studies were initiated to determine the variation in feed efficiency of lactating Holstein cows due to genotype. Data are being collected from several national and international collaborators as part of this project with the eventual goal of developing genomic breeding values for dairy feed efficiency. Events: Results of these studies were reported at the Federation of Animal Science Society meetings. Products: The Spartan Dairy Ration Formulation 3 software continued to be sold as a tool to ensure that scientific findings impact nutritional efficiency on commercial dairy farms. PARTICIPANTS: Partner organizations in studies during the past year include Provimi NA, Wageningen University (The Netherlands), Iowa State University, Virgina Technical University, and University of Wisconsin at Madison. Collaborators at Michigan State University include Drs. Robert Tempelman, Mirian Weber Nielsen, Elizabeth Karcher, Lorraine Sordillo, and Adam Lock. These studies provided opportunity for training five undergraduate students. TARGET AUDIENCES: Target audience includes other dairy scientists, consulting nutritionists and veterinarians. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
In our calf study, we found that supplementation with omega-3 fatty acids tended to decrease the expression of pro-inflammatory cytokines and reduce the temperature increase in response to a Pasteurella vaccine. Results indicate that supplementation may affect the ability of the calves to respond to a disease challenge. Moreover, flax oil seemed to have greater benefit than fish oil. Based on these data, we conclude that omega-3 fatty acids supplementation to young calves has potential for improving health of young milk-fed calves. In our mammary regulation studies, we concluded that acetate upregulates the expression of Acetyl-CoA Carboxylase and Steroyl-CoA Desaturate 1 in MAC-T cells, which indicates that aceate may increase de novo synthesis and desaturation of fatty acids in the bovine mammary gland. Regarding the effect of protein nutrition on lactating cows, we found that not only does a low protein diet down-regulate hepatic genes of protein catabolism and ureagenesis, it increases expression of some genes for transporting amino acids into mammary cells. These include aminopeptidase N and cationic amino acid transporter 1. Understanding how mammary cells adapt to changes in supply of fatty acids and amino acids is a necessary step in enhancing efficiency of milk production.

Publications

• Hill, T.M., VandeHaar, M.J., Sordillo, L.M., Catherman, D.R., Bateman, H.G., and Schlotterbeck,R.L. 2011. Fatty acid intake alters growth and immunity in milk-fed calves. J. Dairy Sci 94:3936-3948.
• Jacobs, A.A.A., Liesman, J.S., VandeHaar, M.J., Dijkstra, J., van Vuuren, A.M., and van Baal, J. 2011. Effects of short- and long-chain fatty acids on expression of lipogenic genes in bovine mammary epithelial cells. J. Anim. Sci. 89(E-Suppl.1):750.
• Karcher, E.L., Hill, T.M., Vito, N., Sordillo, L.M., Bateman, H.G. Schlotterbeck, R.L., and VandeHaar, M.J. 2011. The effect of omega-3 supplementation on the immune response of Holstein calves. J. Anim. Sci. 89(E-Suppl.1):746.
• De Vries, L.D., Casey, T,. VandeHaar, M., and Plaut, K.. 2011. Efects of TGF-β on mammary remodeling during the dry period of dairy cows. J. Dairy Sci. 94:6036-6046.
• Casey, T., Dover, H., Liesman, J., De Vries, L., Kiupel, M., VandeHaar, M., and Plaut, K. 2011. Transcriptome analysis of epithelial and stromal contributions to mammogenesis in three week prepartum cows. PLoS ONE 6(7): e22541. doi:10.1371/journal.pone.0022541
• Davis Rincker, L.E., VandeHaar, M.J., Wolf, C.A., Liesman, J.S., Chapin, L.T., and Weber Nielsen, M.S. 2011. Effect of intensified feeding of calves on growth, pubertal age, calving age, milk yield, and economics. J. Dairy Sci. 94:3554-3567.
• Hill, T.M., VandeHaar, M.J., Sordillo, L.M., Bateman, H.G., and Schlotterbeck, R.L. 2011. Effect of fatty acid intake by dairy calves on performance, health, and markers of immunity. J. Anim. Sci. 89 (E-Suppl.1):263.

Progress 01/01/10 to 12/31/10

Outputs
OUTPUTS: Two studies were conducted in collaboration with Provimi-NA to examine effects of fatty acid supplements on immune function. In the first study, 88 calves were fed milk replacers supplemented with 0 or 1% NeoTec4, a commercially available blend of butyric, coconut, and flax oils. NeoTec4 improved daily gain, feed intake, feed efficiency, and reduced the number of abnormal fecal days. NeoTec4 also lessened the inflammatory response to a challenge with salmonella toxin at 2-wk-old and or Pasturella vaccine at 5-wk-old, as observed by reduced hyperthermia and hypophagia and reduced change in tumor necrosis factor alpha. In addition, NeoTec4 enhanced the response in interleukin-4 post challenge and enhanced titers for BVD and PI3. We conclude that supplementation of milk replacer with a blend of butyrate, coconut and flax oils improves some immune responses, which may partly explain the reduction in scours and concurrent improvements in growth. In the second study, 48 bull calves were fed from 1-wk-old to 5-wk-old with milk replacers based on lard and supplemented with 2% lard, 2% fish oil, or 2% flax oil. Flax oil, but not fish oil, improved body weight gain and hip width gain. The number of abnormal fecal days was not altered except in the first week of feeding, when flax oil reduced it. Flax oil, but not fish oil, reduced the inflammatory response to Pasturella vaccine at 5-wk-old as observed by reduced hyperthermia. Blood was collected at 4-wk-old for measurement of FA profile of PBMC phospholipids and for analyses of expression of genes associated with immune function. These analyses are on-going. PARTICIPANTS: Three undergraduate students who will be attending veterinary school were engaged in learning about nutrition and how nutrition impacts health. TARGET AUDIENCES: Our target audience is farmers, consultants, and other scientists. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Major impacts in the past year include our finding that fatty acid supplements can improve immune functioning of calves, which is currently being applied in commercial milk replacer. Through an improvement in calf health and development, feed efficiency is improved in the dairy industry. Our other major impact was to apply our nutrition model to user-friendly software. The Spartan Dairy Ration Evaluator/Balancer 3.0 program was completed and released for sale in 2010. The program enables evaluation and formulation of diets with the latest research to improve efficiency of feed use on farms.

Publications

• De Vries, L.D., Dover, H., Casey, T., VandeHaar, M., and Plaut, K. 2010. Characterization of mammary stromal remodeling during the dry period. J. Dairy. Sci. 93:2433-2443.
• VandeHaar, M.J., Kriegel, R.D., Bucholtz, H.F., Beede, D.K., Allen, M.S., and Black, J.R. 2010. Spartan Ration Evaluator/Balancer for Dairy Cattle: an agricultural management microcomputer program. Michigan State University, East Lansing.

Progress 01/01/09 to 12/31/09

Outputs
OUTPUTS: 1. Efforts to improve heifer nutrition were continued. A long term study was completed measuring milk production of cows that had been fed 1 of 2 diets as calves before weaning. Diets were a standard milk replacer fed at 1.2% of BW and a high-protein milk replacer at 2.1% of BW. The calves grown more rapidly tended to produce more energy-corrected milk (10,070 vs 9780 kg 305-d projected ECM at P=0.27). If the milk data were adjusted for parent PTA, milk was increased by 4% at P=0.06. Profitability through first lactation tended to be greater (P=0.2) for calves fed for faster gains. 2. Another study was completed to understand mammary remodeling during the dry period. Repeated mammary biopsies were taken from 7 cows around the dry period. Number of activated fibroblasts (those expressing smooth muscle alpha actin) and percent intralobular stromal area were greater (P<0.05) in the early and mid-dry period (when remodeling is active) than in at 1 week before calving (when lactogenesis begins). Expression of transforming growth factor beta 1 (TGFb) decreased (P<0.05) from late lactation to the dry period. Addition of TGFb to explants of biopsied tissue increased the number of activated stromal cells, and this effect was similar for all biopsies. 3. Efforts in nutrition modeling and building practical nutrition software tools were continued. All specifications for the Spartan Dairy ration evaluator/formulator program were completed including an optimizer for comparing feeds and determining cost-effective rations to meet nutrient requirements and minimize P and N losses from farms. The feed intake prediction equation in othe program was validated using 12 groups of high-producing Holstein cows (1068 cows) on 8 Michigan farms. Actual feed intake and composition were measured, as well as body weight and fatness of cows within each pen. Milk records were obtained from DHI. Daily milk production averaged 42 kg and ranged from 30 to 52 kg. The Spartan 3 prediction was better for high-producing cows than the alternatives tested. Work on the stand-alone Spartan Dairy program is only 4 weeks away from final testing. 4. In the past year, I taught a general animal nutrition to 190 students with an emphasis on efficient and sustainable use of resources in animal agriculture. PARTICIPANTS: Dr. Miriam Weber Nielsen was the primary investigator for the calf study and Dr. Karen Plaut was the major investigator for mammary remodeling study. TARGET AUDIENCES: Target audiences were other scientists, extension agents, veterinarians and field nutritionists, students, and farmers. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
1. Regarding heifer nutrition, we found that intensified milk replacer programs may be cost-effective alternatives for raising calves before weaning, especially if milk prices are high. Whether similar results could be obtained from feeding more of a standard milk-replacer or from achieving increased intake of grain is not clear. 2. Regarding changes in the mammary gland in the dry period, our results are consistent with the idea that TFG beta 1 is a major regulator of mammary remodeling in cows and that it might be useful in trying to achieve maximum milk yield in shortened dry period systems. 3. Regarding the Spartan 3 program, the model is now serving as the platform for the NC-1040 regional meeting as we strive to develop mechanistic models of metabolism and the stand-alone program is used in teaching. Due to budget restrictions and potential loss of programmer support, we may decide to forgo releasing the program for use on farms and only use it in-house.

Publications

• Autken, S. K., Karcher, E. L., Rezamand, P., Gandy, J. C., VandeHaar, M. J., Capuco, A. V., and Sordillo, L. M. 2009. Evaluation of antioxidant and proinflammatory gene expression in bovine mammary tissue during the periparturient period. J Dairy Science 92: 589-598.
• Baik, M., Etchebarne, B. E., Bong, J. and VandeHaar, M. J. 2009. Gene Expression Profiling of Liver and Mammary Tissues of Lactating Dairy Cows. Asian-Aust. J. Anim. Science 22: 871-881.

Progress 01/01/08 to 12/31/08

Outputs
OUTPUTS: 1. In the past year, I did a sabbatic in the Netherlands for 6 months with partial support as a Fulbright scholar for teaching and research. While there, I learned about the Dutch dairy cow nutrition model and about life cycle analysis and optimization for sustainability, taught nutritional genomics of dairy cattle to PhD students, gave three seminars on nutritional efficiency of dairy cows to scientific groups and another seminar on mammary development of heifers, and discussed ideas and planned projects related to protein metabolism and nutrition modeling. 2. In the past year, we continued efforts on understanding the molecular controls of the efficiency of N use in lactating cows. Samples of liver tissue from cows fed 11, 15, or 19% CP diets for 12 days in a replicated 3x3 Latin square had previously been analyzed by microarray. In on-going work on the project, we analyzed these samples by Q-PCR for transcripts of 20 different regulatory proteins. We also continued work on understanding the regulation of involution and mammogenesis in dairy cattle during the dry period. 3. Efforts in nutrition modeling and building practical nutrition software tools for farmers were continued. The Spartan Dairy 3 program is now a stand-alone database program that has been used in class but is not yet released. Most of our work in 2008 centered on developing a linear program for least cost ration balancing and feed cost sensitivity. The model also exists as an excel program that includes the complete NRC feed library, NRC nutrition model, our edits to the NRC model, and the working linear program. This model was presented at the NC-1040 regional meeting and will serve as the new nutrition model for the group's activities as we strive to develop mechanistic models of metabolism. 4. In the past year, I taught a general animal nutrition to 206 students with an emphasis on efficient and sustainable use of resources in animal agriculture. PARTICIPANTS: Dr. Karen Plaut was the major investigator for the work on the regulation of mammary remodeling in the dry period. TARGET AUDIENCES: Target audiences were other other scientists, extension agents, veterinarians and field nutritionists, students, and farmers. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
1. Regarding the molecular controls of the efficiency of N use in lactating cows, we found very little evidence for transcriptional control of liver protein metabolism. No changes in transcripts, even for the urea cycle enzymes, were seen, despite major shifts in the efficiency of protein use. 2. Among some of the changes to the NRC model, that we have made in our Spartan nutrition model are lower digestibility discount at high intakes, a lower energy value for digestible protein, adjustments to NDF digestibility that are independent of lignin concentration, lower digestibility of fat for most feeds, a smaller fat-correction for TDN in estimating microbial protein synthesis, a lower RDP requirement, and lysine and methionine supply based on the sum of microbial and RUP supplies. Additions to the model include tracking of Forage NDF, Effective NDF, carbohydrate fractions, lipid fractions for saturated, mono-, and poly-unsaturated fatty acids and biohydrogenation potential, estimated N and P excretion, environmental adjustments, and the 1989 NRC energy and protein system.

Publications

• Silva, L. F. P., Etchebarne, B. E., Weber Nielsen, M. S., Liesman, J. S., Kiupel, M., and VandeHaar, M.J. 2008. Intramammary Infusion of Leptin Decreases Proliferation of Mammary Epithelial Cells in Prepubertal Heifers. J Dairy Sci 91: 3034-3044.
• Davis Rincker, L.E., Weber Nielsen, M.S., Chapin, L.T., Liesman, J.S., and VandeHaar, M.J. 2008. Effects of Feeding Prepubertal Heifers a High-Energy Diet for Three, Six, or Twelve Weeks on Feed Intake, Body Growth, and Fat Deposition. J Dairy Sci 91: 1913-1925.
• Davis Rincker, L.E., Weber Nielsen, M.S., Chapin, L.T., Liesman, J.S., Daniels, K.M., Akers, R.M., and VandeHaar, M.J. 2008. Effects of Feeding Prepubertal Heifers a High-Energy Diet for Three, Six, or Twelve Weeks on Mammary Growth and Composition. J Dairy Sci 91: 1926-1935.
• De Vries, L., VandeHaar, M., Casey, T., Petzke, T., Dover, H., Liesman, J., and Plaut, K. 2008. Stromal changes in the bovine mammary gland during involution and mammogenesis. J. Anim. Sci. Vol. 86(E-Suppl. 2): 569.
• Dover, H, VandeHaar, M., Liesman, L., Patel, O., De Vries, L., and Plaut, K. 2008. Serial mammary biopsies in cows do not alter overall milk production. J. Anim. Sci. Vol. 86(E-Suppl. 2): 441.

Progress 01/01/07 to 12/31/07

Outputs
OUTPUTS: Bovine somatotropin (ST) causes dramatic changes in the metabolism of dairy cows, but only a few of the genes involved have been studied. We examined the influence of ST on the expression of 2400 individual genes and gene pathways associated with metabolism and metabolic regulation in adipose tissue of lactating cows. Primiparous Holstein cows were treated with 0 or 29 mg of ST per day, and omental fat was collected at slaughter on day 60. RNA was isolated from adipose tissue of 3 cows treated with ST and from 3 matched controls. To analyze gene expression, we use the bovine metabolism array (BMET) that we have previously developed. Direct comparisons of the treatments were made using two arrays for each cow comparison with a reversal of dye assignments for the second array; a total of 6 arrays were performed. Approximately 9% of the genes were altered at the P < 0.05 level, and the distribution of P-values was highly skewed toward the lower P values, indicating a significant treatment effect. Treatment with ST altered transcript expression (P<0.05) in adipose tissue for 10% of all genes on the BMET array and 20% of those genes categorized as part of energy pathways. ST down-regulated 91 genes and up-regulated 131 genes at P<0.05. Many of the down-regulated genes coded for enzymes associated with oxidation of glucose, acetate, and fatty acids. For example, bST down-regulated expression for 8 of the 11 enzymes needed to oxidize glucose to pyruvate and expression for 8 of 10 enzymes that convert blood acetate or fatty acids to milk triglycerides. ST had no effect on expression of the hormone-sensitive lipase transcript, but it altered expression of several regulatory genes in a manner consistent with increased activity of hormone sensitive lipase and mobilization of fatty acids from adipose tissue. Thus, ST altered expression of metabolic genes in a manner that would explain the decrease in fatty acid synthesis and esterification and increase in mobilization of fatty acids that occurs in adipose tissue during ST administration. We also examined effects of IGF-I, a downstream hormone of ST, on gene expression of a bovine mammary cell line. Several genes were altered in a manner consistent with the observed increase in proliferation seen in mammary cells incubated with IGF-I. Pathway analysis is ongong. PARTICIPANTS: Collaborators included Dr. Myunggi Baik, Chonnam University, South Korea. Part of the project provided an opportunity for training a graduate student, Michael Jacobsen, and a PhD student, Jinjong Bong. TARGET AUDIENCES: Scientists, nutritionists, and farmers.

Impacts
This year we found that somatotropin had major effects on the gene expression of adipose and mammary tissues in a manner that would explain its repartitioning of nutrients toward the mammary gland for milk synthesis. A thorough understanding of these changes will help us establish new targets for improving the efficiency of milk production and altering the composition of milk. In addition, some of these genes may serve as candidates for genotyping cows and selecting cows that use nutrients more efficiently.

Publications

• Baik, M., Liesman, J.L., Etchebarne, B.E., Bong, J., VandeHaar, M.J. 2007. Effect of growth hormone on expression of metabolic genes in adipose tissue of dairy cows. Journal of Animal Science 85(Suppl 1):84.
• VandeHaar, M.J., Bucholtz, H.F., Beede, D.K., Allen, M.S., Kriegel, R.D. 2007. Spartan Dairy Ration Evaluator/Balancer Version 3: A user-friendly, windows-based software program for dairy nutrition management. Journal of Animal Science 85(Suppl 1):604.

Progress 01/01/06 to 12/31/06

Outputs
We examined effects of protein nutrition on expression of genes in liver and mammary tissues. Twelve lactating cows were fed 3 diets containing 11, 15, or 19% protein for 10-day periods in a Latin-square design. Biopsies of liver and mammary tissue were taken on day 10. The low protein diet decreased milk yield 16% but increased the capture of dietary N by 47% and decreased urinary N excretion 67%. Tissues were analyzed using a bovine metabolism microarray chip to determine what genes are up- or down-regulated with the low protein diet. Expression of several liver genes asssociated with protein metabolism was altered. Most notable, high protein upregulated expression of arginosuccinsate synthetase, a key enzyme of the urea cycle. Work is ongoing to examine expression of genes in mammary tissues and confirm findings in liver. We have also completed analysis of effects of somatotropin treatment on expression of genes in adipose tissue of lactating cows. Somatotropin down-regulated many of the key genes associated with lipogenesis and up-regulated those associated with lipolysis, showing that gene transcription is an important part of the somatotropic effect on adipose tissue. We have also continued work on profitable systems for raising dairy heifers and on evaluation and enhancement of nutrition models.

Impacts
Our underlying hypothesis is that we can identify efficient cows by finding specific genes that vary in response to protein and account for much of the variation in N efficiency among cows. Our first step is find out how the gene expression is altered by feeding a low protein diet with the idea that these genes may serve as candidates for genotyping cows. If we can successfully accomplish this long-term goal, we could have a tremendous impact on the emissions of ammonia from dairy farms.

Publications

• VandeHaar, M.J., St-Pierre, N. 2006. Major advances in nutrition: Relevance to the sustainability of the dairy industry. Journal of Dairy Science 89:1280-1291.
• Bartlett, K.S., McKeith, F.K., VandeHaar, M.J., Dahl, G.E., Drackley, J.K. 2006. Growth and body composition of dairy calves fed milk replacers containing different amounts of protein at two feeding rates. Journal of Animal Science 84:1454-1467.
• Schlegel, M.L., Bergen, W.G., Schroeder, A.L., VandeHaar, M.J., Rust, S.R. 2006. Use of bovine somatotropin for increased skeletal and lean tissue growth of Holstein steers. Journal of Animal Science 84:1176-1187.
• Baik, M., Aschenbach, J.R., Liesman, J.S., VandeHaar, M.J. 2006. Effect of dietary protein levels on milk production and nitrogen efficiency in dairy cattle. Journal of Animal Science 84(Suppl 1):81.
• Davis Rincker, L., VandeHaar, M.J., Wolf, C., Liesman, J., Chapin, L., Weber Nielsen, M. 2006. Effects of an intensified compared to a moderate feeding program during the pre-weaning phase on long-term growth, age at calving, and first lactation milk production. Journal of Animal Science 84 (Suppl 1):438.
• Etchebarne, B.E., Silva, L.F.P., Liesman, J.S., VandeHaar, M.J. 2006. Leptin increase IGF-I-induced expression of SOCS3 mRNA in prepubertal heifer mammary parenchyma. Journal of Animal Science 84 (Suppl 1):145.

Progress 01/01/05 to 12/31/05

Outputs
Most work related to this project in the past year has been part of MICL08299 and MICL02034. Our overall hypothesis is that IGF-I stimulates and leptin inhibits mammogenesis in prepubertal heifers. In addition to those projects, we devoted efforts to developing a new bovine long-oligo microarray of about 2400 genes that encode metabolic enzymes, transport proteins, regulatory proteins, receptors, hormones, muscle and milk proteins, and other proteins involved in metabolic regulation. We began work to examine effects of protein nutrition on expression of genes in liver and mammary tissues.

Impacts
Methods to manage heifers that promote high IGF-I and low leptin concentrations in blood might enable heifers to reach calving at an earlier age while promoting healthy mammary gland development; this would improve the efficiency of using protein on a whole farm basis. Methods to determine which cows use N more efficiently could help to improve the environmental sustainability of the dairy industry.

Publications

• Brown, E. G., M. J. VandeHaar, K. M. Daniels, J. S. Liesman, L. T. Chapin, J. W. Forrest, R. M. Akers, R. E. Pearson, and M. S. Weber Nielsen. 2005. Effect of increasing energy and protein intake in heifer calves on mammary development. J. Dairy Sci. 88:595-603.
• VandeHaar, M.J. 2005. Regulation of nutrient partitioning: an overview of the hormones that are affected by nutrition or that directly alter metabolism. Pages 275-289 in Pond, W.G., D. Church, K. Pond, and P. Schoknecht, Basic Animal Nutrition and Feeding, 5th ed., John Wiley & Sons, Inc., Hoboken, NJ.
• VandeHaar, M.J. 2005 Dairy cattle. Pages 413-437 in Pond, W.G., D. Church, K. Pond, and P. Schoknecht, Basic Animal Nutrition and Feeding, 5th ed., John Wiley & Sons, Inc., Hoboken, NJ
• Davis Rincker, L. 2005. Nutritional influences on body and mammary growth and effect of leptin and IGF-I in prepubertal dairy heifers. Ph.D. dissertation. Michigan State University. East Lansing.
• VandeHaar, M.J. 2005. Developments in replacement nutrition. Proc. Michigan Veterinary Conference, Jan 29, Lansing, MI, Michigan State University.
• Brown, E. G., M. J. VandeHaar, K. M. Daniels, J. S. Liesman, L. T. Chapin, D. H. Keisler, and M. S. Weber Nielsen. 2005. Effect of increasing energy and protein intake on body growth and carcass composition of heifer calves. J Dairy Sci 88:585-594.

Progress 01/01/04 to 12/31/04

Outputs
Most work related to this project in the past year has been part of MICL08299 and MICL02034. Our overall hypothesis is that IGF-I stimulates and leptin inhibits mammogenesis in prepubertal heifers. In addition to those projects, we devoted efforts to developing a new bovine long-oligo microarray of 2400 genes that encode metabolic enzymes, transport proteins, regulatory proteins, receptors, hormones, muscle and milk proteins, and other proteins involved in metabolic regulation. We are initiating work to examine effects of protein nutrition on expression of genes in liver and mammary tissues.

Impacts
Methods to manage heifers that promote high IGF-I and low leptin concentrations in blood might enable heifers to reach calving at an earlier age while promoting healthy mammary gland development; this would improve the efficiency of using protein on a whole farm basis.

Publications

• Etchebarne, B.E., Nobis, W., Allen, M.S., VandeHaar, M.J. 2004. Design of a bovine metabolism oligonucleotide gene array. Journal of Animal and Feed Science 13(Suppl. 1):385-388.
• Radcliff, R.P., VandeHaar, M.J., Kobayashi, Y., Sharma, B.K., Tucker, H.A., Lucy, M.C. 2004. Effect of dietary energy and somatotropin on components of the somatotropic axis in holstein heifers. Journal of Dairy Science 87:1229-1235.
• Lew, B.J., Spikovsky, S., Rosa, G.J.M., Liesman, J.S., Radcliff, R.P., Tucker, H.A., Oliveira, M.D.S., VandeHaar, M.J. 2004. Effects of diet and bST on gene expression profile of heifer mammary parenchyma. Journal of Animal Science 82(Suppl 1):393.
• Etchebarne, B.E., Kiupel, M., VandeHaar, M.J. 2004. Characterization of gene expression patterns in bovine mammary epithelial cells isolated using laser capture microdissection. Journal of Animal Science 82(Suppl 1):275.
• Davis, L., Weber Nielsen, M.S., Chapin, L.T., Liesman, J.S., VandeHaar, M.J. 2004. Effects of a high rate of gain for increasing lengths of time on body and mammary growth in prepubertal dairy heifers. Journal of Animal Science 82(Suppl 1):276.
• Beede, D., VandeHaar, M., and Bickert, W. 2004. Opinion: Sustainable Michigan Dairying. Michigan Dairy Review 9:1-2.
• VandeHaar, M.J. 2004. How fast should heifers grow? Proceedings of the Tri-State Dairy Nutrition Conference, ML Eastridge, ed. April 27-28, Ft. Wayne, IN, pp. 91-103. The Ohio State University, Columbus.

Progress 01/01/03 to 12/31/03

Outputs
Most work related to this project in the past year has been part of MICL08299 and MICL02034. Our overall hypothesis is that IGF-I stimulates and leptin inhibits mammogenesis in prepubertal heifers. In the past year, we examined the effects of intramammary infusions of IGF-I and leptin on expression of mammogenic genes. Results so far indicate that IGF-I and leptin alter expression of genes controlling cell proliferative and apoptotic cell signaling pathways in bovine mammary tissue. We also have begun a study to examine the effects of short (3 or 6 week) feeding of a high energy diet on mammary development of prepubertal dairy heifers. Control groups are fed high energy for 12 weeks or low energy for 12 weeks. We also have begun studies to examine effects of bST and energy nutrition on gene expression of mammary epithelial cells using high-density microarrays.

Impacts
Methods to manage heifers that promote high IGF-I and low leptin concentrations in blood might enable heifers to reach calving at an earlier age while promoting healthy mammary gland development.

Publications

• Forrest, J.W., Akers, R.M., Pearson, R.E., Brown, E.G., VandeHaar, M.J., and Weber Nielsen, M.S. 2003. Effects of varying energy intakes on estrogen receptor, cell proliferation, and tissue composition in mammary tissue of pre-pubertal heifers. Journal of Animal Science 81(Suppl. 1):118.
• Forrest, J.W., Akers, R.M., Pearson, R.E., Brown, E.G., VandeHaar, M.J., and Weber Nielsen, M.S. 2003. Effects of varying energy intakes on the deposition of type IV collagen (Col IV) and fibronectin (FN) in the mammary tissue of pre-pubertal heifers. Journal of Animal Science 81(Suppl. 1):300.
• VandeHaar, M.J. 2003. Stewardship: The measure of a good farmer. Michigan Dairy Review 8(4): 1-3.
• Etchebarne, B.E., Silva, L.F.P., Rosa, G.J.M., Coussens, P.M., Weber Nielsen, M.S., VandeHaar, M.J. 2003. Leptin intramammary infusion alters the gene expression profile of prepubertal bovine mammary parenchyma. Journal of Animal Science 81(Suppl. 1):166.
• Etchebarne, B.E., Silva, L.F.P., Rosa, G.J.M., Coussens, P.M., Weber Nielsen, M.S., VandeHaar, M.J. 2003. IGF-I infusion alters gene expression profile of prepubertal bovine mammary parenchyma. Journal of Animal Science 81(Suppl. 1):165.
• Silva, L.F.P., Liesman, J.S., Weber Nielsen, M.S., VandeHaar, M.J. 2003. Intramammary infusion of leptin decreases proliferation of mammary epithelial cells in prepubertal heifers. Journal of Animal Science 81(Suppl. 1):166.
• Suchyta, S.P., Sipkovsky, S., Halgren, R.G., Kruska, R., Elftman, M., Weber-Nielson, M., Vandehaar, M.J., Xiao, L., Tempelman, R.J., Coussens, P.M. 2003. Bovine mammary gene expression profiling using a cDNA microarray enhanced for mammary specific transcripts. Physiological Genomics 16:8-18.
• Etchebarne, B.E., VandeHaar, M.J. 2003. IGF binding protein-2 reduces the mitogenic effect of IGF-I, but not des-IGF-I, in MAC-T bovine mammary epithelial cells. Journal of Animal Science 81(Suppl. 1):308.

Progress 01/01/02 to 12/31/02

Outputs
Most work related to this project in the past year has been part of MICL08257. Our overall hypothesis is that IGF-I stimulates and leptin inhibits mammogenesis in prepubertal heifers. In the past year, we examined the effects of IGF-I and leptin on mammary cell proliferation in vivo. Ten ug of rhIGF-I was infused once per day, via the streak canal, into two quarters, one front and one rear, of six prepubertal dairy heifers. Contralateral quarters received saline with albumin. After 7 d, bromodeoxyuridine (BrdU) was infused intravenously at 5 mg/kg BW, and heifers were slaughtered 2 h later. Samples from three regions of the mammary parenchyma (proximal, intermediate, and distal to the teat) were collected, fixed, sliced, and incubated with BrdU monoclonal antibody to identify cells in the S-phase of the cell cycle. Intramammary infusion of IGF-I increased the percentage of epithelial cells in the S-phase by 60% (6.4 vs. 4.0%, P<0.001). Proliferation was similar (P>0.35) in all three parenchymal regions, and the response to IGF-I was similar in each region, indicating that IGF-I probably translocated homogeneously through the parenchyma. The effect of IGF-I in front quarters was the same as in rear quarters, and infusion of IGF-I in diagonal quarters gave the same response as infusions on the same side, suggesting that each quarter could serve as a separate experimental unit. In a second study, leptin was given by intramammary infusion. Six prepubertal Holstein heifers were fed a low energy diet. The udder of each heifer was blocked into front and rear quarters. The blocks were randomly assigned to receive intramammary infusions of either 0 or 10 ug of rhIGF-I per day and the left or right side within each block was randomly assigned to receive 0 or 100 ug of roLeptin per day (n = 12 quarters) over a 7 d infusion period. There was a significant interaction between leptin and IGF-I treatments (P=0.01). Leptin decreased BrdU-labeling 48% in IGF-I-treated quarters (4.1 vs. 7.9, P<0.01) but decreased BrdU-labeling only 19% in saline-treated quarters (5.0 vs. 6.2, P=0.02). We conclude that local infusion IGF-I increases and leptin decreases proliferation of bovine mammary parenchymal epithelial cells in prepubertal heifers. In other work, we found that increased body fatness of heifers is associated with decreased mammary development. Leptin concentration is highly correlated with body fatness, so this adds support to our idea that leptin inhibits mammogenesis. And in another study, the effect of high energy diets on growth and mammary development of young heifers was examined. We found that feeding calves more milk to promote gains of 700 g/d compared to 400 g/d doubled the amount of parenchymal DNA in the udder. Feeding for faster growth after weaning did not decrease the amount of parenchymal DNA but did increase deposition of mammary fat. Whether the enhanced mammary development before weaning would result in increased milk yield as a cow is not known.

Impacts
Methods to manage heifers that promote high IGF-I and low leptin concentrations in blood might enable heifers to reach calving at an earlier age while promoting healthy mammary gland development.

Publications

• Silva, L. F. P., VandeHaar, M. J., Weber-Nielsen, M. S., Smith, G.W. 2002. Evidence for a local effect of leptin on bovine mammary gland. Journal of Dairy Science 85:3277-3286.
• Silva, L.F.P., VandeHaar, M.J., Whitlock, B.K., Radcliff, R.P., Tucker, H.A. 2002. Short communication: Relationship of body growth to mammary development in dairy heifers. Journal of Dairy Science 85:2600-2602.
• Park, A.F., Shirley, J.E., Titgemeyer, E.C., Meyer, M.J., VanBaale, M.J., and VandeHaar, M.J. 2002. Effect of protein level in prepartum diets on metabolism and performance of dairy cows. Journal of Dairy Science 85:1815-1828.
• Perkins K.H., VandeHaar, M.J., Burton, J.L., Liesman, J.S., Erskine, R.J., and Elsasser, T.H. 2002. 2002. Clinical responses to intramammary endotoxin infusion in dairy cows subjected to feed restriction. Journal of Dairy Science 85:1724-1731.
• VandeHaar, M.J., Silva, L.F.P., Etchebarne, B.E., Weber-Nielsen, M.S. 2002. Potential role for leptin in mammary development of heifers. Journal of Animal Science 80(Suppl.1):80.
• Silva, L.F.P., VandeHaar, M.J., Weber-Nielsen, M.S., Etchebarne, B.E. 2002. Leptin reduces proliferation of a bovine mammary epithelial cell line (MAC-T). Journal of Animal Science 80(Suppl.1):338.
• Brown, E.G., VandeHaar, M.J., Daniels, K.M., Liesman, J.S., Chapin, L.T., Weber-Nielsen, M.S. 2002. Increasing energy and protein intake of Holstein heifer calves increases mammary development. Journal of Animal Sci 80(Suppl.1):80.
• Whitlock, B.K., VandeHaar, M.J., Silva, L.F.P., Tucker, H.A. 2002. Effect of dietary protein on prepubertal mammary development in rapidly-growing dairy heifers. Journal of Dairy Science 85:1516-1525.

Progress 01/01/01 to 12/31/01

Outputs
This project is carried out in conjunction with MICL01521. High energy diets increase serum leptin concentration and decrease mammogenesis in dairy heifers. Using a bovine mammary epithelial cell line (MAC-T), we found that the addition of bovine or ovine leptin, up to 160 ng/ml, to the culture media for 3 days caused a linear decrease in IGF-I-stimulated cell proliferation. Similar results were obtained when cells were stimulated with fetal bovine serum. In both cases, the maximum dose of leptin decreased cell proliferation by about 25%. Using reverse-transcription PCR, we examined the expression of mRNA for leptin receptors in tissues of prepubertal dairy heifers. We were especially interested in determining if mammary tissues expressed the long splice variant (Ob-Rb), which has an intracellular signaling domain essential for leptin's weight-reducing effects in rodents. We detected Ob-Rb mRNA in all tissues examined: hypothalamus, pituitary, heart, spleen, liver, lung, ovary, testis, skeletal muscle, subcutaneous adipose tissue, primary mammary epithelial cells, mammary extra-parenchymal adipose tissue, mammary parenchymal tissue, and in MAC-T cells. The widespread tissue distribution of Ob-Rb in the growing heifer suggests that leptin may have a direct action on peripheral tissues, including the mammary gland. The presence of Ob-Rb mRNA in the mammary epithelium, along with our results in mammary cell cultures, supports the idea that leptin mediates the effects of nutrition on mammogenesis in dairy heifers. This work is further explained in MICL08257. We also found that feeding-induced negative energy balance delays and prolongs the systemic inflammatory response to an intramammary infusion of endotoxin as indicated by responses in body temperature, heart rate, and respiration rate. Negative energy balance also delayed recovery from neutropenia compared with control cows fed for postive energy balance and caused a greater and more sustained CD18 up-regulation on milk neutrophils. Energy balance did not affect the CD62L system in blood or milk. This work is further explained in MICL06900.

Impacts
Metabolic interactions during prepubertal mammary development and during the periparturient period can have significant impacts on the flow of nutrients to the mammary gland during lactation. Better methods for feeding and managing dairy heifers before puberty and dairy cows around the time of calving will improve efficiency of nutrient use on dairy farms and enhance the economic and environmental sustainability of dairy farming.

Publications

• Perkins, K.H., VandeHaar, M.J., Tempelman, R.J., Burton, J.L. 2001. Negative energy balance does not decrease expression of leukocyte adhesion or antigen-presenting molecules in cattle. J Dairy Sci 84:421-428.
• Silva, L.F.P.,VandeHaar, M.J., Weber, M.S. and Smith, G.W. 2001. Leptin receptor expression in the bovine mammary gland and other tissues. J Animal Sci. 79(suppl.1):225.
• Wolf, C.A., and VandeHaar, M.J. 2001 Economics of dairy heifer growth programs. J Animal Sci. 79(suppl.1):224.

Progress 01/01/00 to 12/31/00

Outputs
Work on this project in the past year focused mostly on the relationship between heifer growth and subsequent milk production and on mechanisms whereby nutrition alters mammary development. Most research supports the idea that high energy intake impairs mammary development of heifers. High energy intake increases growth rate, and the rapid growth rate is often considered to be the cause of mammary impairment. High energy intake also increases body fatness, and we found that body fatness might be more important than rapid growth in the etiology of impaired heifer mammary development. This fits with our novel proposal that leptin, a peptide produced by adipose tissue, inhibits mammary development. We found leptin receptors in mammary tissue and mammary epithelial cells of heifers. Currently, we are determining if leptin inhibits proliferation of primary mammary epithelial cells in culture. Through a better understanding of the factors that control mammary development of heifers, we should be able to reduce age at first calving while maintaining high milk production and thus enhance the overall efficiency of nutrient use and the profitability of dairy farms.

Impacts
The PI has given several invited presentations in the past three years related to this project with the most recent at an international meeting in the Netherlands. Our ration balancing software, which was partly a result of work in this project area, is used world-wide by more than 4500 consultants and farmers. Our results have been reported in the Michigan Dairy Review to all dairy farmers in the state.

Publications

• Radcliff, R.P., VandeHaar, M.J., Chapin, L.T., Pilbeam, T.E., Beede, D.K., Staisiewski, E.P., Tucker, H.A. 2000. Effects of diet and injection of bovine somatotropin on prepubertal growth and first-lactation milk yields of Holstein cows. Journal of Dairy Science 83:23-29.
• VandeHaar, M.J., Silva, L.F.P., Whitlock, B.K., Radcliff, R.P., Tucker, H.A. 2000. Relationship of body growth to mammary development in dairy heifers. Proc 5th Joint EAAP/ASAS Workshop on the Biology of Lactation in Farm Animals, Aug. 19, The Hague, The Netherlands, pp. 6-7.
• Vleurick, L., Renaville, R., VandeHaa,r M., Hornick, J.L., Istasse, L., Parmentier, I., Bertozzi, C., Van Eenaeme, C., Portetelle, D. 2000 A homologous radioimmunoassay for quantitation of insulin-like growth factor binding protein-2 in blood from cattle. Journal of Dairy Science 83:452-458.

Progress 01/01/99 to 12/31/99

Outputs
Work on this project in the past year focused mostly on the relationship between heifer growth and subsequent milk production and on mechanisms whereby nutrition alters mammary development. We found that increasing dietary protein from 14 to 19% does not have a major effect on mammary development of rapidly-grown prepubertal heifers. We also found that insulin-like growth factor (IGF) binding protein (BP)-2 inhibits IGF-induced proliferation of the MAC-T mammary epithelial cell line. In addition, we found that leptin, an endocrine produced by adipose tissue, inhibits proliferation of these cells. Currently, we are determining if leptin inhibits proliferation of primary mammary epithelial cells. Such an inhibition would help explain why heifers grown rapidly have decreased mammary development. Through a better understanding of the factors that control mammary development of heifers, we should be able to reduce age at first calving while maintaining high milk production and thus enhance the overall efficiency of nutrient use and the profitability of dairy farms.

Impacts
The PI has given several invited presentations in the past three years related to this project. Our ration balancing software, which was partly a result of work in this project area, is used world-wide by more than 4000 consultants and farmers. Our results have been reported in the Michigan Dairy Review to all dairy farmers in the state.

Publications

• 1. VandeHaar MJ, Sharma BK, Radcliff R, Renaville R, Lucy M, Tucker H. 1999 Effects of dietary energy and somatotropin (bST) on the somatotropic axis in dairy heifers and relationships to body and mammary development. S Afr J Anim Sci 29(ISRP):286-287.
• 2. Silva LFP, VandeHaar MJ 1999 Role of leptin in mammary cell proliferation. S Afr J Anim Sci 29(ISRP):300-301.
• 3. Whitlock BK. 1999. Influence of dietary protein on prepubertal mammary gland development in rapidly-grown dairy heifers. M.S. Thesis, Michigan State University.
• 4. Whitlock BK, VandeHaar MJ, Tucker HA 1999 Influence of dietary protein on prepubertal mammary gland development in rapidly-grown heifers. J Dairy Sci 82(Suppl 1):51.

Progress 01/01/98 to 12/31/98

Outputs
Work on this project in the past year focused mostly on the relationshiop between heifer growth and subsequent milk production. In conjuction with Dr. H.A. Tucker, we determined that heifers that were grown rapidly had decreased milk production in their first lactation even though their diet before puberty was high in protein as well as energy. In that study, 105 Holstein heifers were assigned to 1 of 3 treatments. They were fed a control diet to gain fed either a control diet to gain 0.8 kg/d (n = 35, LC) or a diet higher in protein and energy to gain 1.2 kg/d (n = 35, HC). Thirty-five heifers were fed the high protein, high energy diet and injected daily with bST at 25 ug/kg BW intramuscularly; HB. Heifers were eligible to be bred once they weighed 363 kg. Heifers were fed their respective diet and HB heifers were injected with bST until confirmed pregnant. All pregnant heifers were commingled and fed a common diet until parturition. Heifers in HC and HB groups had significantly greater average daily gains (ADG) than the LC group (1.13 and 1.15 vs. 0.78 kg/d, respectively) until confirmed pregnant. The high protein, high energy diet reduce age at first calving 3 months but also significantly reduced average daily milk production over the first 270 d from 29.1 to 25.6 kg/d. The high diet plus bST reduced age at first calving 3 months without a significant reduction in milk yield compared to the controls (26.9 vs. 29.1 kg/d). Through a better understanding of the factors that control mammary development of heifers, we should be able to reduce age at first calving while maintaining high milk production and thus enhance the overall efficiency of nutrient use and the profitability of dairy farms.

Impacts
(N/A)

Publications

• VandeHaar, M.J. 1998 Nutritional factors and lactation. in Knobil E, Neill JD, Encyclopedia of Reproduction, Academic Press, San Diego.
• VandeHaar, M.J. 1998 Efficiency of nutrient use and relationship to profitability on dairy farms. J Dairy Sci 81:272-282.
• Radcliff, R., VandeHaar, M., Chapin, L., Pilbeam, T., Ashley, R., Puffenbarger, S., Stanisiewski, E., Beede, D., and Tucker, H.. 1998 Effects of diet and exogenous bST on reproductive performance of dairy heifers. J Dairy Sci 81(Suppl 1):227.
• Radcliff, R., VandeHaar, M., Chapin, L., Pilbeam, T., Ashley, R., Puffenbarger, S., Stanisiewski, E., Beede, D., and Tucker, H.. 1998 Effects of diet and exogenous bST on growth and lactation of dairy heifers. J Dairy Sci 81(Suppl 1):227.
• Ying, Y., Allen, M., VandeHaar, M., and Ames, K. 1998. Effects of fineness of grinding and conservation method of corn grain on ruminal and whole tract digestibility and ruminal microbial protein production of Holstein cows in early lactation. J Dairy Sci 81(Suppl 1):339.
• Ying, Y., Allen, M., VandeHaar, M., and Ames, K. 1998. Effects of fineness of grinding and conservation method of corn grain on ruminal and whole tract digestibility and ruminal microbial protein production of pregnant Holstein heifers. J Dairy Sci 81(Suppl 1):339.
• VandeHaar, M.J. 1998. Accelerated Growth Strategies for Dairy Heifers: Protein and energy requirements for rapid heifer growth. J Dairy Sci 81:1195.

Progress 01/01/97 to 12/31/97

Outputs
In studies examining the relationship of prepartum diets to health and production of dairy cows after calving, we found that feeding diets with added "anionic salts" (such as calcium chloride and magnesium sulfate) to cows before calving decreased urine pH and improved calcium homeostasis at calving but also decreased feed intake and decreased energy balance of cows. We concluded that heifers should not be fed anionic salts, and that when feeding anionic salts to cows, their use should be limited to that needed to lower urine pH to 6.2. In a separate study, I analyzed published data to determine if differences in dietary protein would account for some of the variation in mammary development when heifers are fed for gains more rapid than 900 g/d. In some studies, rapidly-grown heifers had only 40% the mammary development of control heifers and in others mammary development was normal. Differences in the ratio of protein to energy in the diet accounted for 75% of this variation. I concluded that inadequate protein might have been responsible for the impaired mammary development of rapidly-grown heifers in most published reports.

Impacts
(N/A)

Publications

• RADCLIFF, R.P., VANDEHAAR, M.J., SKIDMORE, A.L., CHAPIN, L.T., RADKE, B.R., LLOYD, J.W., STAISIEWSKI, E.P., TUCKER, H.A. 1997. Effect of diet and bST on heifer growth and mammary development. Journal of Dairy Sci 80:1996-2003.
• VANDEHAAR, M.J.. 1997. Dietary protein and mammary development of heifers: analysis from literature data. Journal of Dairy Science 80 (Suppl. 1):216.
• VANDEHAAR, M.J., ALLEN, M.A. 1997. Approaches to the next NRC: protein nutrition for lactating cows. Journal of Dairy Science 80 (Suppl. 1):256.
• BEEDE, D.K., VANDEHAAR, M.J. 1997. Approaches to the next NRC: dry cow nutrition. Journal of Dairy Science 80 (Suppl. 1):256.
• MOORE S.J., VANDEHAAR, M.J., SHARMA, B.K., PILBEAM, T.E., BEEDE, D.K., BUCHOLTZ, H.F., LIESMAN, J.S., HORST, R.L., GOFF, J.P. 1997. Varying dietary cation anion difference (DCAD) for dairy cattle before calving. Journal of Dairy Science 80 (Suppl. 1):170.
• VANDEHAAR, M.J. 1997. Feeding dairy heifers for lifelong profit. Proceedings of the Southwest Nutrition Conference, February 27, Phoenix, AZ.

Progress 01/01/96 to 12/30/96

Outputs
In a field study of more than 1500 cows, those with elevated concentrations of non- esterified fatty acids (NEFA) and depressed concentrations of insulin-like growth factor- I (IGF-I) in blood before calving have a greater incidence of peripartum health problems. Farm management which favors increased feed intake (plenty of bunk space per cow and feed available for most of the day) was associated with a lower incidence of displaced abomasum. Other diseases are being examined.

Impacts
(N/A)

Publications

• Yung MC, VandeHaar MJ, Fogwell RL, Sharma BK. 1996 Effect of energy balance and somatotropin on insulin-like growth factor-I in serum and on weight and progesterone of corpus luteum in heifers. J Animal Sci 74:2239.
• Schemmel RA, Kras K, Cotten N, Suziki K, Sharma BK, VandeHaar MJ. 1996 Fischer 344 rats are the same weight but are fatter than S5B/P1Ras rats fed a high fat diet. Nutr Research 16:1225.
• Liesman JL, Sharma BK, Dyk PB, VandeHaar MJ, Emery RS. 1996 Relation of periparturient diseases to prepartum concentrations of insulin-like growth factor-I and NEFA in Holstein dairy cows. J Dairy Sci 79(Suppl.1):189.
• VandeHaar MJ. 1996 Efficiency of nutrient use and relationship to profitability on dairy farms. J Dairy Sci 79 (Suppl.1).

Progress 01/01/95 to 12/30/95

Outputs
The response in serum insulin-like growth factor-I (IGF-I) concentrations to administration of bST and ST-releasing factor is not a good indicator of the galactopoietic response in lactating cows. We conclude that the classical somatomedin hypothesis of bST action is not adequate to explain the regulation of milk production in cattle. In other experiments, we found that cows with elevated non-esterified fatty acids (NEFA) in blood before calving have a greater incidence of peripartum health problems. By feeding diets more concentrated in energy and protein we were able to decrease NEFA concentrations and increase IGF-I concentrations in blood before calving and to decrease liver fat at calving.

Impacts
(N/A)

Publications

• VANDERKOOI, W.K., VANDEHAAR, M.J., et al. 1995. Comparison of somatotropin releasing factor and somatotropin: the somatotropic axis in lactating primiparous cows. J Dairy Sci 78:2140.
• BINELLI, M., VANDERKOOI, W.K., VANDEHAAR, M.J., et al. 1995. Comparison of somatotropin releasing factor & somatotropin: body growth & lactation in primiparous cows. J Dairy Sci 78:2129.
• TUCKER, H.A., TERHUNE. A.L.F., et al. 1995. Long-term somatotropic & galactopoietic effects of a (1-30) NHEt analog of growth hormone releasing factor. J Dairy Sci 78:1489.
• DYK, P.B., EMERY, R.S., LIESMAN, J.L., et al. 1995. Prepartum non-esterified fatty acids in plasma are higher in cows developing periparturient health problems. J Dairy Sci 78(Suppl.1):264.
• VANDEHAAR, M.J., SHARMA, B.K. et al. 1995. Prepartum diets more nutrient- dense than recommended by NRC improve nutritional status of peripartum cows. J Dairy Sci 78(Suppl.1):264.
• SHARMA, B.K., et al. 1995. Prepartum diets more nutrient-dense than recommended by NRC do not enhance milk yield or alter body weight in dairy cows postpartum. J Dairy Sci 78(Suppl.1):265.
• VANDEHAAR, M.J. 1995. Optimum level of milk production: nutritional aspects. Proc Tri-State Dairy Nutrition Conference, Fort Wayne, IN, p. 135.

Progress 01/01/94 to 12/30/94

Outputs
Long-term goal is to improve the efficiency by which nutrients are used to produce milk and meat protein. Our approach in the past year has been to determine if diets fed to dairy cows before calving will impact the health and production of dairy cows during the subsequent lactation. Eighty cows were fed diets of varying energy density from 1.32 to 1.62 Mcal NE/kg for at least the last 20 days prepartum, and all cows were fed a diet balanced for high production after calving. All cows consumed more NE than required according to NRC, 1989, and even those on low energy diets consumed 17 Mcal per day during the last 2 wk of gestation. Dietary energy intake increased linearly as dietary energy density increased. Furthermore, preliminary data indicate that as dietary energy density increased, cows had slightly lower concentrations of non-esterified fatty acids and greater concentrations of insulin-like growth factor-I in plasma during the last 2 wk of gestation, indicating that they were in better nutritional status. Nonetheless, milk production was not altered. Liver fat content is being assessed. In a separate study, blood samples have been collected from 100 Michigan farms to examine the relationship between prepartum concentrations of non-esterified fatty acids and insulin-like growth factor-I and health and productivity after parturition. ===.

Impacts
(N/A)

Publications

Progress 01/01/93 to 12/30/93

Outputs
We examined expression of insulin-like growth factor-I (IG-I), a major regulatorof protein synthesis and milk secretion, in cattle. Specifically, we quantified IGF-I and IGF binding proteins in serum and mRNA for IGF-I, St- receptor, and IGF-I receptor in liver and mammary tissue. Feeding growing steers 18% vs. 12% protein had no effect on these measures, and injections of ST in steers stimulated IGF-I expression similarly for the two dietary groups. In a separate study, lactating dairy cows were infused with growth hormone releasing factor (GRF) to give ST concentrations similar to those of cows treated with exogenous ST. Infusions of GRF resulted in greater stimulation of liver IGF-I mRNA, serum IGF-I, and serum IGF-binding protein-3 than ST infusion but similar stimulation of milk yield. We conslude, that although IGF-I expression can be suppressed by undernutrition, it is not enhanced by extra protein, and that enhanced IGF-I expression may not result in further production responses once a threashold level has been achieved. In other studies, we observed decreases in the concentraitons of serum IGF-I and IGF binding protein-3 and increases in serum free fatty acids as dairy cows approached parturition, possible indicating that they were in negative energy balance despite the calculated value being positive. Finally, we completed a nutrition model for dairy cattle and released it as a computer software program for balancing diets.

Impacts
(N/A)

Publications

Progress 01/01/92 to 12/30/92

Outputs
The expression of insulin-like growth factor-I (IGF1), a major regulator of protein synthesis and milk secretion, was examined in cattle in various states of energy balance (EB). Cows in early lactation (negative EB) had lower serum IGF1 and IGF binding protein-3 concentrations, lower liver IGF1 mRNA expression, and slightly greater mammary IGF1 mRNA expression than cows in late lactation. Heifers in negative EB had less serum IGF1 and liver IGF1 mRNA and smaller corpora lutea than heifers in positive EB. These results indicate that IGF1 may mediate the inhibitory effects of negative EB on reproductive efficiency. In addition, EB had no effect on IGF1 mRNA expression by the corpus luteum, indicating that reduced local synthesis of IGF1 does not mediate the effect of negative EB on luteal function. Therefore, although we previously found that autocrine/paracrine IGF1 may be as important as endocrine IGF1 for growth, we conclude that, for ovarian function, endocrine IGF1 is most important and that, for milk secretion, autocrine/paracrine IGF1 may be important in early lactation. In a separate study, we found that a 16% CP diet was adequate to achieve gains of 909 g/d in 5 mo-old Holstein heifers and that 19% CP did not increase gains or alter serum IGF1 concentration. We conclude that NRC protein requirements are adequate for young calves.

Impacts
(N/A)

Publications

• VANDEHAAR MJ, SHARMA BK, FOGWELL RL 1992 Diet restriction of heifers decreases concentrations of insulin-like growth factor I (IGF-I) in serum, IGF-I mRNA in liver, and luteal weight. J Animal Sci 70(suppl.1):274.
• GROSHKO VL, SHARMA BK, VANDEHAAR MJ 1992 Effect of feeding protein in excess of National Research Council requirements on growth performance and serum insulin-like growth factor-I concentrations of young Holstein heifers. J Animal Sci.

Progress 01/01/91 to 12/30/91

Outputs
The somatomedin/IGF-I hypothesis of somatotropin (ST) action is that ST increases serum insulin-like growth factor-I (IGF-I) which, in turn, increases milk secretion. We are trying to determine why serum IGF-I is lowest in early lactation when milk yield is highest in light of this hypothesis. We found that BST significantly increased milk yield, serum IGF-I, and liver IGF-I mRNA expression in late lactation cows, consistent with the idea that IGF-I mediates the effect of BST. As expected, cows in early lactation compared to cows in late lactation produced more milk, were in negative energy balance, and had lower serum IGF-I concentrations. However, liver IGF-I mRNA expression was not different between early and late lactation cows. We conclude that synthesis of IGF-I is not decreased but rather that IGF-I clearance from serum may be increased during early lactation.

Impacts
(N/A)

Publications

• VANDEHAAR, M.J., MOATS-STAATS, B.M., DAVENPORT, M.L., WALKER, J.L., KETESLEGERS, J.M. SHARMA, B.K., UNDERWOOD, L.E. 1991. Reduced serum IGF-I concentrations in protein-restriction growing rats are accompanied by reduced IGF-I mRNA levels i.
• SHARMA, B.K., VANDEHAAR, M.J. 1991. Effects of exogenous bovine somatotropin and stages of lactation on IGF-I mRNA abundance in the liver of dairy cows. J. Dairy Sci. 74(suppl 1):224.
• VANDEHAAR, M.J., SHARMA, B.K. 1991. Dietary protein restriction decreases IGF-I mRNA abundance of skeletal muscle in growing rats. J. Anim Sci 69(suppl 1):100.

Progress 01/01/90 to 12/30/90

Outputs
IGF-I mRNA was detected in bovine liver and mammary tissues, and studies are being conducted to analyze IGF-I mRNA concentrations in tissues at various stages of lactation. In growing rats, we have found that low protein diets decrease the abundance of IGF-I mRNA in muscle and liver and that the body weight gain of these rats was more closely correlated with muscle IGF-I mRNA abundance than with serum IGF-I concentrations. These results indicate that autocrine/paracrine actions of IGF-I may be more important for growth than endocrine actions. Future studies with growing ruminants must focus on understanding the regulation of muscle IGF-I synthesis in addition to serum IGF-I concentrations.

Impacts
(N/A)

Publications

• NO PUBLICATIONS REPORTED THIS PERIOD.