Effects of a 6-wk intraduodenal supplementation with quercetin on energy metabolism and indicators of liver damage in periparturient dairy cows.

Periparturient dairy cows experience metabolic challenges that result in a negative energy balance (EB) and a range of postpartum health problems. To compensate for the negative EB, cows mobilize fatty acids from adipose tissues, which can lead to fatty liver disease, a periparturient metabolic disorder. Flavonoids, such as quercetin (Q), are polyphenolic substances found in all higher plants and have hepatoprotective potential and the ability to prevent or reduce lipid accumulation in the liver. In ruminants, few studies on the metabolic effects of Q are available, and thus this study was conducted to determine whether Q has beneficial effects on EB, lipid metabolism, and hepatoprotective effects in periparturient dairy cows. Quercetin was supplemented intraduodenally to circumvent Q degradation in the rumen. Cows (n=10) with duodenal fistulas were monitored for 7wk. Beginning 3wk before expected calving, 5 cows were treated with 100mg of quercetin dihydrate per kilogram of body weight daily in a 0.9% sodium chloride solution for a total period of 6wk, whereas the control cows received only the sodium chloride solution. The plasma flavonoid levels were higher in the Q-treated cows than in the control cows. A tendency for higher postpartum (pp) than antepartum (ap) plasma flavonoid levels was observed in the Q-treated cows than in the controls, which was potentially caused by a reduced capacity to metabolize Q. However, the metabolic status of the Q-treated cows did not differ from that of the control cows. The pp increases in plasma aspartate aminotransferase and glutamate dehydrogenase activities were less in the Q-treated cows than in the control cows. The Q had no effect on energy expenditures, but from ap to pp the cows had a slight decline in respiratory quotients. Irrespective of the treatment group, the oxidation of fat peaked after calving, suggesting that the increase occurred because of an increased supply of fatty acids from lipomobilization. In conclusion, supplementation with Q resulted in lower pp plasma aminotransferase and glutamate dehydrogenase, which indicated reduced liver damage. However, the direct effects of Q on the liver and the implications for animal performance remain to be investigated.

Reduced AgRP activation in the hypothalamus of cows with high extent of fat mobilization after parturition.

Agouti-related protein (AgRP), produced by neurons located in the arcuate nucleus of the hypothalamus stimulates feed intake. During early lactation dairy cows increase their feed intake and additionally mobilize their fat reserves leading to increased plasma non-esterified fatty acid (NEFA) concentrations. Since cows with a higher extent of fat mobilization exhibit the lower feed intake, it seems that high NEFA concentrations confine hyperphagia. To test the involvement of AgRP neurons, we investigated 18 cows from parturition until day 40 postpartum (pp) and assigned the cows according to their NEFA concentration on day 40pp to either group H (high NEFA) or L (low NEFA). Both groups had comparable feed intake, body weight, milk yield, energy balance, plasma amino acids and leptin concentrations. Studies in respiratory chambers revealed the higher oxygen consumption and the lower respiratory quotient (RQ) in H compared to L cows. mRNA abundance of neuropeptide Y, peroxisome proliferator-activated receptor-gamma, AMP-activated protein kinase, and leptin receptor in the arcuate nucleus were comparable between groups. Immunohistochemical studies revealed the same number of AgRP neurons in H and L cows. AgRP neurons were co-localized with phosphorylated adenosine monophosphate-activated kinase without any differences between groups. The percentage of cFOS-activated AgRP neurons per total AgRP cells was lower in H cows and correlated negatively with oxygen consumption and NEFA, positively with RQ, but not with feed intake. We conclude that AgRP activation plays a pivotal role in the regulation of substrate utilization and metabolic rate in high NEFA dairy cows during early lactation.

Plasma ghrelin is positively associated with body fat, liver fat and milk fat content but not with feed intake of dairy cows after parturition.

Ghrelin is a gastrointestinal peptide hormone that is present in blood mostly in a non-posttranslationally modified form, with a minor proportion acylated at Ser(3). Both ghrelin forms were initially assigned a role in the control of food intake but there is accumulating evidence for their involvement in fat allocation and utilization. We investigated changes in the ghrelin system in dairy cows, exhibiting differences in body fat mobilization and fatty liver, from late pregnancy to early lactation. Sixteen dairy cows underwent liver biopsy and were retrospectively grouped based on high (H) or low (L) liver fat content post-partum. Both groups had a comparable feed intake in week -6 (before parturition) and week 2 (after parturition). Only before parturition was preprandial total ghrelin concentration higher in L than in H cows and only after parturition was the basal plasma concentration of non-esterified fatty acids higher in H than in L cows. Both before and after parturition, H cows had higher preprandial plasma concentrations of acyl ghrelin, a higher acyl:total ghrelin ratio, lower plasma triacylglyceride concentrations and a lower respiratory quotient compared with L cows. These group differences could not be attributed to an allelic variant of the acyl ghrelin receptor. Rather, the ratio of acyl:total ghrelin correlated with several aspects of fat metabolism and with respiratory quotient but not with feed intake. These results show that endogenous ghrelin forms are associated with fat allocation, fatty liver, and utilization of fat during the periparturient period.