Feed and energy intake of ruminant animals can change dramatically in response to changes in diet composition or metabolic state, and such changes are poorly predicted by traditional models of feed intake regulation. Recent work suggests that temporal patterns of fuel absorption, mobilization, and metabolism affect feed intake in ruminants by altering meal size and frequency. Research with nonruminants suggests that meals can be terminated by signals carried from the liver to the brain via afferents in the vagus nerve and that these signals are affected by hepatic oxidation of fuels and generation of ATP. We find these results consistent with the effects of diet on feed intake of ruminants. Of fuels metabolized by the ruminant liver, propionate is likely a primary satiety signal because its flux to the liver increases greatly during meals. Propionate is utilized for gluconeogenesis or oxidized in the liver and stimulates oxidation of acetyl CoA. Although propionate is extensively metabolized by the ruminant liver, there is little net metabolism of acetate or glucose, which may explain why these fuels do not consistently induce hypophagia in ruminants. Lactate is metabolized in the liver but has less effect on satiety, probably because of greater latency for reaching the liver within meals and because of less hepatic extraction compared with propionate. Hypophagic effects of fatty acid oxidation in the liver are likely from delaying hunger rather than promoting satiety because beta-oxidation is inhibited during meals by propionate. A shortage of glucose precursors and increased fatty acid oxidation in the liver for early lactation cows lead to a lack of tricarboxylic acid (TCA) cycle intermediates, resulting in a buildup of the intracellular acetyl-CoA pool and export of ketone bodies. In this situation, hypophagic effects of propionate are likely enhanced because propionate entry into the liver provides TCA cycle intermediates that allow oxidation of acetyl-CoA. Oxidizing the pool of acetyl-CoA rather than exporting it increases ATP production and likely causes satiety despite the use of propionate for glucose synthesis. A better understanding of metabolic regulation of feed intake will allow diets to be formulated to increase the health and productivity of ruminants.

For dairy cattle, the first several weeks of lactation represent the highest-risk period in their lives after their own neonatal period. Although more than 50% of cows during this period are estimated to suffer from at least one subclinical disorder, the complicated admixture of normal adaptations to lactation, infectious challenges, and metabolic disorders has made it difficult to determine which physiological processes are adaptive and which are pathological during this time. Subacute inflammation, a condition that has been well documented in obesity, has been a subject of great interest among dairy cattle physiologists in the past decade. Many studies have now clearly shown that essentially all cows experience some degree of systemic inflammation in the several days after parturition. The magnitude and likely persistence of the inflammatory state varies widely among cows, and several studies have linked the degree of postpartum inflammation to increased disease risk and decreased whole-lactation milk production. In addition to these associations, enhancing postpartum inflammation with repeated subacute administration of cytokines has impaired productivity and markers of health, whereas targeted use of nonsteroidal anti-inflammatory drugs during this window of time has enhanced whole-lactation productivity in several studies. Despite these findings, many questions remain about postpartum inflammation, including which organs are key initiators of this state and what signaling molecules are responsible for systemic and tissue-specific inflammatory states. Continued in vivo work should help clarify the degree to which mild postpartum inflammation is adaptive and whether the targeted use of anti-inflammatory drugs or nutrients can improve the health and productivity of dairy cows.

. 2005. Strong relationships between mediators of the acute phase response and fatty liver in dairy cows. Can. J. Anim. Sci. 85: [165][166][167][168][169][170][171][172][173][174][175]. The objective of this study was to investigate the relationship between activation of acute phase response and fatty liver in transition dairy cows. Fatty liver was induced in dairy cows by feeding 8 kg of cracked corn 1 mo before the expected day of parturition. Liver and blood samples were obtained at days -4, 3, 8, 12, 14, 22, 27, and 36 postpartum. Cows that developed fatty liver (n = 4) reached peak total lipids in the liver at day 12 postpartum with 11.4% (wet wt.) compared with 6.6% in control cows (n = 4). Cows with fatty liver had greater plasma tumor necrosis factor-alpha (TNF-α), nonesterified fatty acids (NEFA), and lower lactate concentrations than did control cows at day -4. During highest concentrations of total lipids in the liver, for at least one time-point, fatty-liver cows had greater concentrations of plasma serum amyloid A (SAA), haptoglobin, and NEFA and lower concentrations of calcitonin gene-related peptide (CGRP), prostaglandin E 2 (PGE 2 ), cortisol, and TNF-α than did control cows. Concentrations of total lipids in the liver at 12 d postpartum were correlated (a) positively with plasma TNF-α, SAA, and NEFA and negatively with plasma CGRP before calving, (b) positively with plasma SAA, haptoglobin, and NEFA and negatively with plasma PGE 2 , CGRP, total cholesterol, and glucose at days 3, 8, and 12 postpartum, and (c) negatively with concentrations of plasma glucose, lactate, and total bilirubin after day 12 postpartum. In conclusion, this study indicates that the acute phase response occurs in cows with fatty liver as well as strong relationships between mediators of immune response and fatty liver. Mots clés: Réponse phase aiguë, foie gras, vaches laitièresFatty liver is a common metabolic disorder that affects almost half of all dairy cows immediately after parturition.Despite much progress in understanding metabolic events during the development of fatty liver, the precise mechanisms of the pathology remain unclear. The conventional view is that fatty liver is characterized by excess liver triacylglycerols (TAG) arising from a negative energy balance after parturition (Bauchart et al. 1998). The negative energy balance evokes a major mobilization of non-esterified fatty acids (NEFA) from adipose tissue and increased uptake of

Previous research has shown that postpartum administration of the nonsteroidal antiinflammatory drug (NSAID) sodium salicylate can increase 305-d milk yield in older dairy cattle (parity 3 and greater). However, in this prior work, sodium salicylate was delivered to cows via the drinking water, a method that does not align well with current grouping strategies on commercial dairy farms. The objective of the current study was to replicate these results on a commercial dairy farm with a simplified treatment protocol and to compare sodium salicylate with another NSAID, meloxicam. Dairy cattle in their second lactation and greater (n=51/treatment) were alternately assigned to 1 of 3 treatments at parturition, with treatments lasting for 3d. Experimental treatments began 12 to 36 h after parturition and were (1) 1 placebo bolus on the first day and 3 consecutive daily drenches of sodium salicylate (125 g/cow per day; SAL); (2) 1 bolus of meloxicam (675 mg/cow) and 3 drenches of an equal volume of water (MEL); or (3) 1 placebo bolus and 3 drenches of water (CON). Blood samples were collected on the first day of treatment, immediately following the last day of treatment, and 7d after the last day of treatment; plasma was analyzed for glucose, β-hydroxybutyrate (BHB), free fatty acids, haptoglobin, and paraoxonase. Milk production, body condition score, reproductive status, and retention in the herd were monitored for 365 d posttreatment, and effects of treatment, parity, days in milk, and interactions were evaluated in mixed effects models. Significance was declared at P<0.05. Whole-lactation milk and protein yields were greater in NSAID-treated cows, although 305-d fat production was not affected. There was a significant interaction of treatment and parity for plasma glucose concentration; MEL increased plasma glucose concentrations compared with CON and SAL in older cows. Sodium salicylate decreased plasma BHB concentration compared with MEL at 7d posttreatment, although no difference was detected immediately following treatment. Haptoglobin concentrations were elevated in SAL cows compared with CON. There was a tendency for CON cows to be removed from the herd more quickly than MEL cows (42 vs. 26% at 365 d posttreatment). Body condition score, concentrations of plasma free fatty acids and paraoxonase, and time to pregnancy were not affected by treatment. These results indicate that NSAID administration in postpartum cows has the potential to be a viable way to improve productivity and potentially longevity in commercial dairies, although further research is necessary to optimize recommendations for producers.

Animal models have been invaluable for studying aspects of food intake regulation that for various reasons cannot be observed in humans. The dairy cow is a unique animal model because of an unrivaled energy requirement; its great drive to eat results in feeding behavior responses to treatments within the physiological range. Cows' docile nature and large size make them ideal for measuring temporal treatment effects because digestion and absorption kinetics and responses in endocrine systems, gene expression, metabolite pools and fluxes, and feeding behavior can be measured simultaneously. Thus, cows are important models to investigate interactions of short-term signals regulating food intake. Furthermore, different physiological states throughout the lactation cycle provide powerful models to study how short- and long-term signals interact to affect long-term energy status. The use of the cow as a model can lead to breakthroughs in understanding the complex interactions of signals regulating food intake.