Temporal effects of ruminal infusion of propionic acid on hepatic metabolism in cows in the postpartum period

Abstract

A faster rate of infusion of propionic acid into the rumen of cows in the postpartum period increased meal size compared with a slower rate of infusion in a previous experiment. Because propionate is anaplerotic and stimulates oxidation of acetyl coenzyme A (CoA) in the liver, and hepatic oxidation has been linked to satiety, this result was opposite to our expected response. We then hypothesized that the faster rate of infusion might have saturated the pathway for propionate metabolism in hepatocytes resulting in lower first-pass extraction by the liver. Because we were measuring feeding behavior, we could not sample blood and liver tissue over time in that experiment. Therefore, to determine the temporal effects of propionic acid (PA) infusion on hepatic metabolism and plasma metabolites over the time course of a meal, we infused 1.25 mol of PA (2.5 L of 0.5M PA) over 5 min (FST) or 15 min (SLW) into the rumen. We evaluated response to PA infusions both before feeding, when ruminal PA production by rumen microbes is lower and hepatic acetyl CoA concentration is greater, and 4 h after feeding, when PA production is greater and hepatic acetyl CoA concentration is lower. Blood and liver samples were collected before, and after 5, 15, and 30 min of infusion. Contrary to our hypothesis, the rate of PA infusion into the rumen did not affect plasma propionate concentration, indicating the FST effects on feeding behavior were not because of a limitation on propionate uptake by the liver. However, FST increased plasma glucose and insulin concentrations faster than SLW, resulting in a reduction in plasma nonesterified fatty acid concentration during the time frame of meals. Decreased plasma nonesterified fatty acid concentration during infusion likely decreased the supply of acetyl CoA for oxidation in the liver. The FST treatment also increased fumarate concentration at 5 min after the initiation of infusion but did not affect oxaloacetate concentration compared with SLW, consistent with a limitation to propionate metabolism at that reaction. A metabolic bottleneck at the malate dehydrogenase reaction for FST compared with SLW would further contribute to a reduction in hepatic oxidation within the time frame of a meal, allowing greater meal size, consistent with the hepatic oxidation theory and our previous results.