Source: KANSAS STATE UNIV submitted to
METABOLIC RELATIONSHIPS IN SUPPLY OF NUTRIENTS FOR LACTATING COWS (NC-1009)
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
0211772
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
NC-1040
Project Start Date
Oct 1, 2007
Project End Date
Sep 30, 2013
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
KANSAS STATE UNIV
(N/A)
MANHATTAN,KS 66506
Performing Department
Animal Science & Industry
Non Technical Summary
Modern dairy cows are capable of producing enormous amounts of milk; the average dairy cow in the United States now produces nearly 20,000 pounds of milk in a lactation, containing approximately 2,400 pounds of milk solids. Even more amazing is the fact that the cow must synthesize all of the glucose required for milk component synthesis and body maintenance. Not surprisingly, insufficient glucose production can be a serious problem for these high-producing cows. One of our goals is to explain why fatty liver, a common disorder in dairy cattle, makes cows less capable of producing glucose. If we can clearly explain the mechanism for this response, we may be able to devise strategies to increase glucose production, allowing for greater milk production and improved metabolic health. Among the most economically important factors determining dairy farm income is production of milk components, and milk fat production is the most highly variable component of milk. Within the last decade, one pathway for altering milk fat synthesis has been described; however, there are likely to be other factors which influence secretion of milk fat. Therefore, our second aim is to evaluate a potential mechanism regulating transfer of fatty acids from the blood to the mammary gland, mediated by a newly-discovered circulating protein. If this protein does influence milk fat production, we can build upon our understanding of how diet and metabolic state influence milk component production, allowing us to manage dairy cattle more carefully to maintain milk fat yield.
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
30734991060100%
Goals / Objectives
To quantify properties of feeds that determine the availability and utilization of nutrients critical to milk production. To quantify metabolic and molecular interactions that alter synthesis of milk components. To use this knowledge of feed properties and metabolic and molecular quantitative relationships to challenge and refine precision feeding systems for dairy cattle
Project Methods
Fatty liver is a condition that is common among dairy cows in early lactation, and it has been associated with decreased production of glucose, an essential precursor of milk lactose and an important fuel in the mammary gland. Despite mounting evidence that fatty liver suppresses gluconeogenesis, there is currently no mechanism to explain this potential connection. Recently, relationships between tumor necrosis factor alpha (TNF) and liver lipid content have indicated that inflammation may be involved in the pathology of this disorder. To assess the potential role of TNF in fatty liver and associated complications, we will measure effects of exogenous TNF administration on glucose production and liver lipid accumulation in lactating cows. If TNF decreases glucose synthesis and/or increases liver lipid accumulation compared to pair-fed controls, it will provide the first direct evidence that TNF is capable of inducing symptoms of fatty liver in ruminants. This is expected to lead to further investigations into the role of inflammation during the per parturient period and potential interventions to prevent metabolic disorders. Despite progress in our understanding of milk fat depression in recent years, few factors that influence milk fat production have been described. Much research has focused on synthesis of fatty acids by the mammary gland, but in the bovine, approximately 50% of milk fatty acids are derived from plasma lipids. These preformed fatty acids are primarily mobilized from plasma triglycerides, raising the possibility that mammary lipoprotein lipase activity may be an important control point for milk fat production. A recently-discovered plasma protein, fasting-induced adipocyte factor (FIAF) is capable of altering body composition by increasing fatty acid oxidation and by directly inhibiting lipoprotein lipase; however, the impact of this peptide on lactating animals has not been investigated. Secretion of FIAF by adipose tissue increases during fasting, and increased FIAF may contribute to hyperlipidemia during negative energy balance by limiting utilization of plasma triglycerides. In addition, gastrointestinal microbes have been shown to suppress expression of FIAF by the large intestine. This novel host/microbe interaction may play an important role in ruminants, which rely so heavily on microbial metabolism for their energy requirements. We will investigate the role of FIAF in dairy cattle by first measuring mRNA and protein abundance throughout the gastrointestinal tract and in liver and adipose tissue. Secondly, we will infuse exogenous FIAF into lactating cows for 48 hours to assess effects on metabolic parameters and milk fat production. We expect FIAF to increase plasma triglycerides and reduce milk fat production by inhibiting lipoprotein lipase activity. If FIAF has important effects on milk fat production, it may provide a novel mechanism for diet or metabolic state to alter milk composition.

Progress 10/01/07 to 09/30/13

Outputs
Target Audience: Our target audience is primarily dairy nutritionists and veterinarians who formulate diets for dairy producers, as well as the dairy producers themselves. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Two graduate students gained experience with a wide variety of nutritional and physiology research methods by conducting this study with the mentorship of the principle investigator and collaborators. How have the results been disseminated to communities of interest? Presentations were given at the 2013 annual meeting of the American Dairy Science Association, and manuscripts derived from this work are currently under review. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Major activities completed: A study was conducted to evaluate the impact of chromium propionate, bypass amino acids, and their interactions on productivity, metabolic function, and immune function in peak lactation dairy cattle. Specific objectives met: Our study addressed objective 1 of the project: To quantify properties of feeds that determine the availability of nutrients critical to milk production. Significant results achieved: Dietary chromium propionate promotes increased productivity in first-lactation cows near peak lactation, and may also influence immune function. Key outcomes: Our results highlight poorly-understood impacts of the trace mineral chromium on immune function.

Publications

  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Brake, D. W., E. C. Titgemeyer, M. J. Brouk, C. A. Macgregor, J. F. Smith, and B. J. Bradford. 2013. Availability to lactating dairy cows of methionine added to soy lecithins and mixed with a mechanically extracted soybean meal. J. Dairy Sci. 96(5):3064-74. Farney, J. K., L. K. Mamedova, J. F. Coetzee, B. KuKanich, L. M. Sordillo, S. K. Stoakes, J. E. Minton, L. C. Hollis, and B. J. Bradford. 2013. Anti-inflammatory salicylate treatment alters the metabolic adaptations to lactation in dairy cattle. Am J Physiol Regul Integr Comp Physiol. 305(2):R110-7. Hawkins, A., K. Yuan, C. K. Armendariz, G. Highland, N. M. Bello, T. Winowiski, J. S. Drouillard, E. C. Titgemeyer, and B. J. Bradford. 2013. Effects of urea formaldehyde condensation polymer treatment of flaxseed on ruminal digestion and lactation in dairy cows. J Dairy Sci. 96(6):3907-15. Mullins, C.R., D. Weber, E. Block, J.F. Smith, M.J. Brouk, and B. J. Bradford. 2013. Short communication: Supplementing lysine and methionine in a lactation diet containing a high concentration of wet corn gluten feed did not alter milk protein yield. J Dairy Sci. 96(8):5300-5.


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

Outputs
OUTPUTS: A meta-analysis of published studies was conducted to determine the effects of dietary sugar on production outcomes in lactating dairy cattle, and to assess possible interactions with other dietary factors. PARTICIPANTS: Participants: Chad Mullins, Laman Mamedova, Mike Brouk, Evan Titgemeyer, Chris Reinhardt, Karl Yuan, Shih-Hui Li. Collaborators: Joe Harner, Dept. of Bio. Ag. Engineering, KSU; Duy Hua, Dept. Chemistry, KSU; J. Yu, Dept. Chemistry, KSU; Jeff Firkins, Ohio State University; Chel Moore, Elanco Animal Health; Howard Green, Elanco Animal Health; Kelly Perfield, Elanco Animal Health; John Smith, University of Arizona; Gina Pighetti, University of Tennessee; Mike Allen, Michigan State University. TARGET AUDIENCES: Our target audience is primarily dairy nutritionists and veterinarians who formulate diets for dairy producers, as well as the dairy producers themselves. PROJECT MODIFICATIONS: No significant changes.

Impacts
The combined results of the 18 treatment comparisons included in this study suggested that supplemental sugar tended to increase dry matter intake by 0.38 kg/d, with a 95% likelihood that the true mean response lies somewhere between a decrease of 0.04 kg/d and an increase of 0.80 kg/d. Despite the finding that feed intake tends to increase with sugar supplementation, there was no evidence that dietary sugar increased milk production, protein content, or energy-corrected milk production. However, the meta-analysis did identify a tendency for supplemental sugar to increase milk fat content by 0.085 percentage units. This finding is consistent with recent reports suggesting that sugar can help to mitigate milk fat depression. Additionally, an interaction between forage neutral detergent fiber (fNDF) concentration and the amount of added sugar influenced feed intake response. In diets with low fNDF content (i.e. a low-forage diet), adding progressively more sugar (from 2% up to 5% of diet dry matter) decreases the feed intake response. Conversely, in a diet with high fNDF content, adding progressively more sugar increases the feed intake response. These findings point to an opportunity to further investigate whether dietary sugar is particularly useful in high-forage lactation diets.

Publications

  • Mullins, C. R., L. K. Mamedova, M. J. Brouk, C. E. Moore, H. B. Green, K. L. Perfield, J. F. Smith, J. P. Harner, and B. J. Bradford. 2012. Effects of monensin on metabolic parameters, feeding behavior, and productivity of transition dairy cows. J. Dairy Sci. 95(3):1323-36.
  • Allen, M. S. and B. J. Bradford. 2012. Control of food intake by metabolism of fuels: a comparison across species. Proc. Nutr. Soc. 71(3):401-9.
  • Mamedova, L. K., E. C. Titgemeyer, G. M. Pighetti, J. Y. Lu, D. H. Hua, and B. J. Bradford. 2012. GPR109A mediates calcium mobilization induced by BHBA in isolated bovine monocytes. J. Dairy Sci. 95 (Suppl. 2): 261-2 (Abstr.).
  • Vargas, C. F., C. D. Reinhardt, J. L. Firkins, and B. J. Bradford. 2012. Meta-analysis of the effects of dietary sugar on intake and productivity of dairy cattle. J. Dairy Sci. 95 (Suppl. 2): 433 (Abstr.).
  • Yuan, K., L. K. Mamedova, S. H. Li, and B. J. Bradford. 2012. Identification of short-chain fatty acid (SCFA) receptor transcripts in ruminal papillae and responses to SCFA infusion. J. Dairy Sci. 95 (Suppl. 2): 568 (Abstr.).


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

Outputs
OUTPUTS: Multiparous Holstein cows were used to determine the effects of monensin (400 mg/cow daily) during the transition to lactation. Cows were randomly assigned, based on calving date, to control or monensin treatments (n = 16 per treatment) 21 d before their expected calving date, and cows remained on treatments through 21 d postpartum. Feeding behavior and water intake data were collected daily. Liver biopsies were conducted after assessing BCS and BW on d -21, -7, 1, 7, and 21 relative to calving for analysis of triglyceride (TG) content as well as mRNA abundance of cytosolic phosphoenolpyruvate carboxykinase (cPEPCK), carnitine palmitoyltransferase 1a (CPT1a), and apolipoprotein B (Apo B). Blood samples were collected 21, 7, and 4 d before expected calving and 1 (day of calving), 4, 7, 14, and 21 d postpartum for nonesterified fatty acid (NEFA), β-hydroxybutyrate (BHBA), glucose, insulin, and haptoglobin analyses. Ruminal pH was collected every 5 min on d 1 through 6 postpartum via a wireless indwelling probe. On d 7 postpartum, a caffeine clearance test was performed to assess liver function. PARTICIPANTS: Barry Bradford, Scott Morey, Shih-Hui Li, Tiffany Lee, Jaymelynn Farney, Cheryl Armendariz, Laman Mamdova, Evan Titgemeyer, Chris Reinhardt, David Anderson. Collaborators: Chel Moore, Kelly Perfield, Howard Green, Elanco Animal Health; Juan Loor, University of Illinois; Doug Mashek, University of Minnesota. TARGET AUDIENCES: Target audiences include dairy producers, nutritionists, veterinarians, and academics working in the area of endocrinology and metabolism. PROJECT MODIFICATIONS: No significant changes

Impacts
Results of our research suggest that monensin may be an effective tool to promote more consistent feed intake patterns and to prevent liver lipid accumulation in transition cows. This information can contribute to a decrease in the incidence of common metabolic disorders in early lactation.

Publications

  • Lee, T. L., D. U. Thomson, B. W. Wileman, L. K. Mamedova, B. J. Bradford, and C. D. Reinhardt. 2011. The effects of anabolic growth implant and restricted feed intake on proliferation of bovine primary skeletal muscle cells. J Dairy Sci. 94 (E-Suppl. 1): 489 (Abstr.).
  • Li, S. H., B. J. Bradford, and L. K. Mamedova. 2011. Effects of volatile fatty acid infusions on angiopoietin-like protein 4 concentration in plasma and ruminal papillae of cattle. J Dairy Sci. 94 (E-Suppl. 1): 731 (Abstr.).
  • Khan, J., D. Graugnard, D. H. Keisler, B. J. Bradford, L. K. Mamedova, J. K. Drackley, and J. J. Loor. 2011. Hepatokine, growth hormone, and PPARα-regulated gene network expression in liver of peripartal cows fed two levels of dietary energy prepartum. J Dairy Sci. 94 (E-Suppl. 1): 732 (Abstr.).
  • Mamedova, L. K., D. G. Mashek, and B. J. Bradford. 2011. Toll-like receptor 4 (TLR4) mediates the induction of cPEPCK expression by palmitate in HepG2 cells. FASEB J. 25:722.10 (Abstr.).
  • Morey, S. D., L. K. Mamedova, D. E. Anderson, C. K. Armendariz, E. C. Titgemeyer, and B. J. Bradford. 2011. Effects of encapsulated niacin on metabolism and production of periparturient dairy cows. J Dairy Sci. 94(10):5090-104.
  • Titgemeyer, E. C., L. K. Mamedova, K. S. Spivey, J. K. Farney, and B. J. Bradford. 2011. An unusual distribution of the niacin receptor in cattle. J Dairy Sci. 94(10):4962-7.
  • Titgemeyer, E. C., K. S. Spivey, L. K. Mamedova, and B. J. Bradford. 2011. Effects of pharmacological amounts of nicotinic acid on lipolysis and feed intake in cattle. Int J Dairy Sci. 6(2):134-41.
  • Bradford, B. J. 2011. The endocrine network: a growing list of hormones regulating transition cow metabolism. Proc. California Anim. Nutr. Conf., May 4-5, 2011. Fresno, CA.
  • Mullins, C. R., L. K. Mamedova, M. J. Brouk, C. E. Moore, H. B. Green, K. L. Perfield, J. F. Smith, J. P. Harner, and B. J. Bradford. 2011. Effects of monensin on metabolic parameters, feeding behavior, and productivity of transition dairy cows. J Dairy Sci. 94 (E-Suppl. 1): 179 (Abstr.).
  • Bradford, B. J., L. K. Mamedova, and D. G. Mashek. 2011. Palmitate promotes fatty acid uptake by HepG2 cells through activation of toll-like receptor 4. Keystone Symposium on Type 2 Diabetes, Insulin Resistance and Metabolic Dysfunction, Keystone, CO. Abstr. 116.


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

Outputs
OUTPUTS: We conducted a study to compare two commercially available acidified by-products for their effects on peripartum serum calcium concentrations, pre and postpartum feed intake, milk production, and postpartum health disorders in dairy cattle. Diets differed in dietary cation-anion difference (DCAD) and source of anionic supplement. Treatments were control (target DCAD +20 meq/100 g DM; n=9 cows, n=4 heifers), BioChlor (target DCAD -10 meq/100 g DM; n=8 cows, n=6 heifers), and SoyChlor (target DCAD -10 meq/100 g DM; n=9 cows, n=6 heifers). Results were presented at the 2010 joint meeting of the American Dairy Science Association / American Society of Animal Science. PARTICIPANTS: Barry Bradford (PI) developed project and carried out data analysis. Laman Mamedova (Research Assistant Professor) coordinated sample analyses. Chad Mullins and D.J. Rezac (Graduate Students) conducted studies and wrote publications. Collaborators included Dr. Evan Titgemeyer, Dr. David Anderson, and Dr. Mike Brouk from Kansas State University. TARGET AUDIENCES: Our target audiences are primarily ruminant nutritionists and veterinarians. Our presentation at the major dairy science meeting in 2010 exposed this work to a large number of these individuals, both nationally and internationally. PROJECT MODIFICATIONS: None

Impacts
Serum calcium concentrations did not differ between dietary treatments and only tended to be different (P = 0.07) over time; values were not indicative of hypocalcemia. With limited sample size, no significant effects of treatment were detected for incidence of postpartum health disorders or plasma BHBA concentration. Although DMI tended to be depressed in the prepartum period by SoyChlor, this intake depression was not accompanied by negative effects on performance or health in the postpartum period. Results suggest that cows were not adequately stressed to cause hypocalcemia and/or DCAD values near 0 were insufficient to improve postpartum health and performance.

Publications

  • Mullins, C.R., Grigsby, K.N., Anderson, D.E., Titgemeyer, E.C., and Bradford, B.J. 2010. Effects of feeding increasing levels of wet corn gluten feed on production and ruminal fermentation in lactating dairy cows. J Dairy Sci. 93: 5329-5337.
  • Mullins, C.R. and Bradford, B.J. 2010. Effects of a molasses-coated cottonseed product on diet digestibility, performance, and milk fatty acid profile of lactating dairy cattle. J Dairy Sci. 93: 3128-3135.
  • Mamedova, L.K., Robbins, K., Johnson, B.J., and Bradford, B.J. 2010. Tissue expression of angiopoietin-like protein 4 in cattle. J Anim Sci. 88: 124-30.
  • Rezac, D.J., Block, E., Weber, D., Brouk, M.J., and Bradford, B.J. 2010. Effects of acidified by-products and pre-partum DCAD onserum calcium, post-partum health and performance when fed to prepartum transition dairy cows. J Dairy Sci. 93(E-Suppl. 1): 780 (Abstr.).
  • Rezac, D.J., Grigsby, K.N., and Bradford, B.J. 2010. Effects of varying inclusion rates of prairie hay and wet corn gluten feed on productivity of dairy cows. J Dairy Sci. 93 (E-Suppl. 1): 515 (Abstr.).


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

Outputs
OUTPUTS: Angiopoietin-like protein 4 (Anglptl4) is a plasma protein that stimulates the oxidation of fatty acids and inhibits fat accumulation. We conducted 2 studies using samples from collaborators at other institutions to determine how energy supply and diet digestibility influence production and secretion of this protein. Plasma, liver, adipose tissue, and ruminal tissue samples were analyzed for Angptl4 mRNA and protein abundance by quantitative real-time PCR and Western blot methods, respectively. Results were presented at the 2009 joint meeting of the American Dairy Science Association / American Society of Animal Science, and also at the International Symposium on Ruminant Physiology in Clermont-Ferrand, France. PARTICIPANTS: Individuals - Barry Bradford (PI): Developed project and carried out data analysis. Liaman Mamedova (Research Assistant Professor): Conducted and coordinated sample analyses. Collaborators - Dr. Masahito Oba, University of Alberta, Canada Dr. Greg Penner, University of Alberta, Canada Dr. Karen Beauchemin, Agriculture and Agri-Food Canada Dr. Kevin Harvatine, Pennsylvania State University Dr. Yves Boisclair, Cornell University, NY TARGET AUDIENCES: Our target audiences are primarily ruminant nutritionists and physiologists. Our presentations at 2 major conferences in the past year exposed this work to a large number of these scientists, both nationally and internationally. PROJECT MODIFICATIONS: None

Impacts
Under-feeding lactating dairy cattle significantly decreased plasma Angptl4 concentration, and the primary tissue responses to under-feeding were decreased adipose tissue mRNA abundance and increased liver mRNA abundance. These data suggest that bovine Angptl4 is not "fasting-induced" as originally described in rodents. In addition, feeding a low-concentrate diet to non-lactating dairy cows tended to increase ruminal tissue Angptl4 mRNA by 120% (P = 0.08) compared to a high-concentrate diet, although no effect on protein abundance was detected. Transcript abundance tended to correlate with mean ruminal pH (P = 0.07) and was inversely correlated with total volatile fatty acid concentration (P = 0.03). In a third study, feeding growing heifers a low-concentrate diet increased ruminal tissue Angptl4 protein abundance (P < 0.001), and a positive relationship with ruminal pH was also observed (P < 0.01). These findings suggest that increased ruminal fermentation results in decreased expression of Angptl4 in ruminal tissue.

Publications

  • Bradford, B. J., L. K. Mamedova, K. J. Harvatine, and Y. R. Boisclair. 2009. Plasma angiopoietin-like protein 4 concentration is decreased by energy restriction in lactating dairy cattle. Proc. XIth International Symposium on Ruminant Physiology, Clermont-Ferrand, France: 426-7 (Abstr.).
  • Mamedova, L. K., G. B. Penner, K. A. Beauchemin, M. Oba, and B. J. Bradford. 2009. Production of angiopoietin-like protein 4 in ruminal tissue is decreased with increasing dietary fermentability. J Dairy Sci. 92 (E-Suppl. 1): 149 (Abstr.).


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

Outputs
OUTPUTS: FIAF (or angiopoietin-like 4) is a plasma protein that stimulates the oxidation of fatty acids and inhibits fat accumulation. The gastrointestinal tract appears to play an important role in regulating plasma FIAF concentration in some situations, and gastrointestinal microbes can influence FIAF production by the gut. Our aim was to determine tissue expression of FIAF in the bovine. Rumen, omasum, abomasum, duodenum, jejunum, ileum, colon, pancreas, liver and adipose tissue samples were collected postmortem from 2 steers for analysis of FIAF messenger RNA abundance and protein content. We are currently analyzing samples shared by collaborators from 2 universities to better understand how diet and physiological state influence FIAF synthesis. Our initial results were presented in a poster at Experimental Biology 2008, a meeting attended by over 13,000 scientists. PARTICIPANTS: Individuals - Barry Bradford (PI): Developed project and carried out data analysis. Liaman Mamedova (Research Assistant Professor): Conducted and coordinated sample analyses. Collaborators - Dr. Masahito Oba, University of Alberta, Canada Dr. Kevin Harvatine, Cornell University, NY Dr. Yves Boisclair, Cornell University, NY. Training - This project has provided research training opportunities for a summer veterinary research scholar and 2 undergraduate students. TARGET AUDIENCES: Our target audiences are primarily ruminant nutritionists and physiologists studying host/microbe interactions. We chose to present our initial findings at Experimental Biology because of the ability to reach both groups. PROJECT MODIFICATIONS: We initially planned to generate recombinant bovine FIAF for use in infusion experiments and to produce an antibody for bovine FIAF detection. However, FIAF proved to be a difficult protein to produce by recombinant methodology, and it took nearly 12 months for a small amount of protein to be delivered from the commercial molecular biology company that handled the task. This delay prevented us from conducting the infusion experiments that we proposed. Fortunately, we were able to validate an anti-human FIAF antibody for use in bovine samples, allowing us to move forward on the characterization portion of the project. We plan to begin experiments utilizing the recombinant FIAF protein soon.

Impacts
FIAF mRNA was quantified by qPCR, and was most abundant in liver (420 arbitrary units; AU) and adipose tissue (320 AU). We detected FIAF mRNA throughout the gastrointestinal tract, with values ranging from 10 AU in the abomasum to 28 AU in the duodenum. By Western blot, FIAF protein was most abundant in liver and adipose tissue. However, FIAF protein was barely detectable in the rumen or duodenum, but was highly abundant in the omasum. Finally, cross-sections of the rumen wall were used for immunohistochemistry staining, and strong signals for FIAF were detected in the epithelial layer. These findings suggest that host/microbe interactions may influence FIAF expression in the ruminant gastrointestinal tract, and make it possible that diet affects ruminant physiology in part by altering gut secretion of FIAF.

Publications

  • Mamedova, L., B. Bradford, K. Robbins, and B. Johnson. 2008. Tissue expression of fasting-induced adipocyte factor in cattle. FASEB J. 22:1116.2 (Abstr.).