Progress 12/01/03 to 11/30/06
Outputs
Aim 1. Glucose demand was increased by injecting phlorizin in a crossover experiment using 12 late-lactation cows (Bradford and Allen, 2005). Phlorizin caused a loss of 474 g glucose/d in urine and stimulated hepatic gluconeogenesis, as evidenced by increased mRNA abundance for 3 potentially rate-limiting gluconeogenic enzymes. However, neither feed intake nor feeding behavior were significantly altered by phlorizin, possibly because phlorizin also stimulated lipolysis, increasing delivery of FA to the liver. In a follow-up study, this lipolytic response was evident in early lactation cows as well, indicating that the presence of a catabolic state could not eliminate the confounding effects of phlorizin on lipid metabolism (Bradford and Allen, 2006). Aim 2. We directly tested the ability of phlorizin to lessen the hypophagic response to propionate in a 2x2 factorial design. As expected, intraruminal propionate infusion decreased feed intake, but phlorizin treatment had
no effect on this response (Bradford and Allen, 2007). Aim 3. Thirty-two lactating Holstein cows were utilized in a crossover experiment with dietary treatments that differed only in dietary starch fermentability. High-moisture corn (highly fermentable) decreased feed intake 2.0 kg/d (P < 0.001) relative to dry, ground corn (less fermentable), consistent with prior observations. Increased starch fermentability also tended to decrease milk fat production (P = 0.06), and milk fat depression was dramatic in cows producing less than ~40 kg/d fat-corrected milk. Milk fat depression was highly correlated with greater concentrations of trans C18:1 FA in milk of low-producing cows fed the high moisture corn diet (Bradford and Allen, 2004). Additionally, propionate challenge tests conducted during a pre-trial period were used to evaluate the effects of propionate on plasma leptin concentrations. Leptin concentrations were decreased during the first 100 min following propionate infusion (P <
0.05), suggesting that the hypophagic effects of propionate are not mediated by leptin (Bradford, Oba, et al. 2006). We were unable to identify clear predictors of individual responses to propionate supply, despite the statistical power of a 32-cow crossover, suggesting that more mechanistic experiments are warranted. We conclude that short-term increases in glucose demand do not increase feed intake. One possible explanation is that increased delivery of FA to the liver stimulated by phlorizin administration increases hepatic FA oxidation, replacing the ATP that is lost as propionate is diverted from oxidation to glucose production.
Impacts
Fermentation characteristics of diets and pattern of propionate production in the rumen are easily manipulated and a greater understanding of propionate regulation of feed intake will allow diets to be formulated to maximize energy intake and milk yield. This will decrease the proportion of feed resources used to meet maintenance requirements, minimizing excretion of nutrients as waste products. However, despite the large effects of diet fermentability on DMI, no ration formulation program, to our knowledge, currently uses this to predict feed intake, which often limits milk yield. If our results are convincing, we envision that models will be adapted to predict hypophagic potential of diets based on concentration and fermentation rate of starch, which affects propionate flux to the liver following a meal.
Publications
- Bradford, B. J. 2006. Propionate regulation of feed intake. Ph.D. dissertation, Department of Animal Science, Michigan State University.
- Bradford, B. J., Gour, A. D., Nash, A. S., and Allen, M. S. 2006. Propionate challenge tests have limited value for investigating bovine metabolism. J. Nutr. 136:1915-1920.
- Bradford, B. J. and Allen, M. S. 2007. Phlorizin administration did not attenuate hypophagia induced by intraruminal propionate infusion. J. Nutr. (in press).
- Bradford, B. J. and Allen, M. S. 2007. Phlorizin induces lipolysis and alters meal patterns in both early and late lactation dairy cows. J. Dairy Sci. (accepted).
- Bradford, B. J. and Allen, M. S. 2007. Short communication: Rate of propionate infusion within meals does not influence feeding behavior. J. Dairy Sci. (accepted) Allen, M.S. and Bradford, B. J. 2006. From the liver to the brain: increasing feed intake in transition cows. Pp. 115-124. Proc. 68th Meeting of the Cornell Nutrition Conference for Feed Manufacturers, Department of Animal Science, Cornell University, Ithaca, NY 14853-4801.
- Bradford, B. J. and Allen, M. S. 2006. Propionate regulation of feed intake. J. Dairy Sci. 89S:49.
- Bradford, B. J. and Allen, M. S. 2006. Phlorizin administration does not attenuate hypophagia induced by intraruminal Na propionate infusion. J. Dairy Sci. 89S:264.
- Allen, M. S. and Bradford, B. J. 2006. Metabolic regulation of food intake in ruminants. J. Dairy Sci. 89S:120.
- Bradford, B. J. and Allen, M. S. 2006. Propionate regulation of feed intake. J. Dairy Sci. 89S:49.
|
Progress 01/01/05 to 12/31/05
Outputs
Propionate was recently shown to increase leptin synthesis in rodents. To determine if a similar effect occurs in ruminants, propionate was administered to lactating dairy cows. In experiment 1, 31 cows were given an intrajugular propionate bolus (1.04 mmol/kg body weight), increasing plasma propionate from 0.2 to 6.0 mM and plasma insulin from 7 to 80 micro U/mL. Plasma leptin concentration decreased from 2.1 ng/mL before bolus to 2.0 ng/mL after dosing (P < 0.05) with no differences in leptin concentrations at 20, 50, and 100 minutes post-bolus (P > 0.05). In experiment 2, 12 cows were used in a duplicated 6x6 Latin square design to assess the dose-response effect of ruminal propionate infusion on plasma leptin concentration. Iso-osmotic mixtures of sodium propionate and sodium acetate were infused continuously for 18 h (21.7 mmol sodium VFA/min); treatments included 0, 20, 40, 60, 80, or 100% of VFA from propionate. Effects on plasma leptin were assessed at the end
of the 18-h infusions. Increasing the proportion of propionate in the infusate linearly increased plasma propionate concentration from 0.18 to 0.33 mM (P < 0.001) and linearly increased plasma insulin concentration from 6.7 to 9.1 micro U/mL (P < 0.05). However, plasma leptin concentration was not affected by treatment. Propionate does not stimulate leptin secretion in lactating dairy cows.
Impacts
Fermentation characteristics of diets and pattern of propionate production in the rumen are easily manipulated and a greater understanding of propionate regulation of feed intake will allow diets to be formulated to maximize energy intake and milk yield. This will decrease the proportion of feed resources used to meet maintenance requirements, minimizing excretion of nutrients as waste products. However, despite the large effects of diet fermentability on DMI, no ration formulation program, to our knowledge, currently uses this to predict feed intake, which often limits milk yield. If our results are convincing, we envision that models will be adapted to predict hypophagic potential of diets based on concentration and fermentation rate of starch, which affects propionate flux to the liver following a meal.
Publications
- Allen, M.S., Bradford, B.J., Harvatine, K.J. 2005. The cow as a model to study food intake regulation. Ann. Rev. Nutr. 25:523-547.
- Bradford, B. J., Allen. M. S. 2005. Phlorizin administration increases hepatic mRNA abundance for gluconeogenic enzymes but not feed intake in late-lactation dairy cows. J. Nutr. 135:2206-2211.
- Bradford, B. J., Oba, M., Ehrhardt, R., Boisclair, R., Allen, M. S. 2005. Propionate is not an important regulator of plasma leptin in dairy cows. Domest. Anim. Endocrinol. 2005 Jul 4; [Epub ahead of print]
- Bradford, B. J., Allen, M. S., Oba, M., Ehrhardt, R., Boisclair, Y. R. 2005. Propionate does not stimulate lepting secretion in lactating dairy cows. 2005 Experimental Biology meeting abstracts. FASEB J. 19: Abstract #6229.
- Bradford, B. J., OToole, A. D., Nash, A. S., Allen, M. S. 2005. Validation of propionate challenge test methodology. J. Dairy Sci. 88(Suppl. 1):249.
|
Progress 01/01/04 to 12/31/04
Outputs
Flux through gluconeogenic pathways may be an important factor regulating dry matter intake in lactating dairy cows. To determine if increased glucose demand affects intake or hepatic metabolism, lactating Holstein cows were treated with phlorizin or propylene glycol (carrier) for 7-d treatment periods. Twelve multiparous cows (mean 269 d in milk) were randomly assigned to treatment sequence in a crossover design and were adapted to a common diet for 7 days prior to the beginning of the experiment. Phlorizin injected subcutaneously at 4 g/d caused glucose excretion in urine at the rate of 474 g/d. While phlorizin caused a decrease in lactose synthesis and milk production (both P < 0.01), dry matter intake and 3.5% fat-corrected milk production were not altered by treatment. A net deficit of 383 g/d of glucose for phlorizin relative to control was likely replaced through increased gluconeogenic flux. Molar ratio of insulin:glucagon was decreased 17% by phlorizin (P <
0.001) and hepatic phosphoenolpyruvate carboxykinase mRNA abundance tended to increase (P = 0.08). In addition, abundance of pyruvate carboxylase mRNA in liver was greater with phlorizin treatment (P < 0.001), suggesting that retention of glucose precursors may be involved in regulation of gluconeogenesis. Late-lactation dairy cows adapted quickly to an increase in peripheral glucose demand. Adaptation mechanisms likely included enhanced gluconeogenic capacity, while dry matter intake was not immediately altered.
Impacts
Fermentation characteristics of diets and pattern of propionate production in the rumen are easily manipulated and a greater understanding of propionate regulation of feed intake will allow diets to be formulated to maximize energy intake and milk yield. This will decrease the proportion of feed resources used to meet maintenance requirements, minimizing excretion of nutrients as waste products. However, despite the large effects of diet fermentability on DMI, no ration formulation program, to our knowledge, currently uses this to predict feed intake, which often limits milk yield. If our results are convincing, we envision that models will be adapted to predict hypophagic potential of diets based on concentration and fermentation rate of starch, which affects propionate flux to the liver following a meal.
Publications
- Bradford, B. J. and M. S. Allen. 2004. Milk fat responses to a change in diet fermentability vary by production level in dairy cattle. J. Dairy Sci. 2004 87: 3800-3807
- Bradford, B. J. and M. S. Allen. 2004. Increasing glucose demand increases hepatic pyruvate caroxylase mRNA concentration but not feed intake in late-lactation dairy cows. J. Anim. Feed Sci. 13:377-380.
- Bradford, B. J. and M. S. Allen, M. S. 2004. Increasing dietary starch fermentability causes milk fat depression in low-producing, but not high-producing cows. J. Dairy Sci. 87(Suppl. 1):308.
|
|