The negative energy balance of dairy cows in the postpartum period is exacerbated by a suppression in appetite. Metabolic diseases resulting from negative energy balance can decrease milk production, health and fertility, increasing risk of culling. Research suggests that feeding behavior is linked to the oxidation of fuels in the liver and that an increase in oxidation of fuels causes satiety. Propionate derived from the fermentation of starch in the rumen is a major glucose precursor in dairy cows but can also cause hypophagia. Because propionate is anaplerotic, it stimulates the oxidation of fuels in the liver, likely causing the hypophagic effects. In order to determine the role of anaplerotic metabolites and uncouplers of oxidative phosphorylation on hepatic metabolism and feeding behavior in dairy cows, 6 studies were conducted. First, using 8 dairy cows in a duplicated 4x4 Latin square design, the effect of feed status (before or after access to feed) on the hepatic extraction and metabolism of propionate over 20 min was determined. The results indicated that hepatic extraction and metabolism of propionate is very rapid, and that metabolite concentrations were greater after compared with before feeding. Additionally, potential bottlenecks of propionate metabolism were identified. Secondly, a study using hepatic explants incubated in [13C3]sodium propionate was conducted to test the effects of 3 different concentrations of propionate (1, 2 or 4 mM) on propionate metabolism over 60 min. An increased concentration of propionate in the range from 1 - 4 mM resulted in the conversion of propionate to acetyl CoA, likely through pyruvate, and that the acetyl CoA was incorporated into the TCA cycle for oxidation. Additionally, metabolism of [13C3]propionate occurred rapidly with significant increases of 13C enrichment detected within 0.5 min for many metabolites. Furthermore, uncoupling the electron transport chain should affect the metabolism of propionate and the feeding behavior of dairy cows as a result of inefficient oxidation of fuels. The effects of two uncouplers of oxidative phosphorylation, 2,4-dinitrophenol methyl ether (DNPME) and sodium salicylate (SAL), on feeding behavior in dairy cows were determined in 2 experiments. Treatment with DNPME and SAL decreased eating rate in dairy cows over the first 4 h following access to feed. Additionally, DNPME increased meal length over the first 4 h following access to feed. Lastly, an experiment was conducted to determine the effects of DNPME and SAL on metabolism and oxidation of propionate over 60 min using hepatic explants from 8 dairy cows. Neither DNPME nor SAL increased oxidation. The DNPME treatment did not alter metabolism of propionate except for an increase of propionate converted to succinyl CoA, however, SAL decreased glucose synthesis from propionate. From this research, we conclude that hepatic metabolism of propionate occurs rapidly and is likely having effects on feeding behavior within minutes as well. As such, the importance of short-term metabolism in regard to feeding behavior and dry matter intake should be considered in future research. Understanding the mechanisms for metabolic control of feed intake will lead to development of novel nutritional or pharmacological approaches to increase energy intake, health, and milk yield of dairy cows; thus, improving nutrient utilization and sustainability of the dairy industry.
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