Pyruvate and hepatic pyruvate dehydrogenase levels in rat strains sensitive and resistant to dietary obesity.

This study compared the effects of exogenous pyruvate and lactate on the serum levels of pyruvate, lactate, glucose, alanine, and insulin, as well as the activity of hepatic pyruvate dehydrogenase (PDH) in strains of rat that were either sensitive [Osborne-Mendel (OM)] or resistant (S5B/Pl) to high-fat diet-induced obesity. Serum pyruvate and lactate were significantly higher and glucose lower in ad libitum-fed OM rats, but these differences disappeared after an 18-h fast. The increase in pyruvate and lactate after exogenous pyruvate administration was significantly greater in S5B/Pl rats than OM rats. There were no differences in serum alanine with strain or diet. The total PDH activity was similar across strains and diets but the proportion of PDH in its activated form (PDHa) was decreased in ad libitum-fed S5B/Pl rats. Pyruvate injection increased insulin and hepatic PDHa activity in OM rats fed both high- and low-fat diets, but these responses were greatly attenuated or absent in S5B/Pl rats. The data are consistent with the hypothesis that modulation of carbohydrate oxidation by PDH may be related to susceptibility to obesity when rats are fed a high-fat diet.