Effect of palmitate on hepatic biosynthetic functions at hyperthermic temperatures

Livers of fasted rats were perfused for 80 min at 37 degrees-43 degrees C, supplemented with lactate, NH4Cl, and ornithine in the presence or absence of palmitate. Hepatic functional integrity was maintained from 37 degrees to 42 degrees C as assessed by gluconeogenesis, ureogenesis, and O2 consumption. Between 42 degrees and 43 degrees C a sharp decline in biosynthetic function occurred. The sharp decline in biosynthetic function occurred. The ratio of lactate disappearance to glucose formation increased progressively with increasing temperature when compared with the ratio obtained at 37 degrees C. Exogenous palmitate significantly decreased the ratio of lactate disappearance to glucose formation at 43 degrees C. Furthermore, palmitate attenuated the detrimental effects of hyperthermia on gluconeogenesis, ureogenesis, and O2 consumption found in the absence of palmitate. The 3-hydroxybutyrate/acetoacetate ratio progressively decreased as the liver temperature was increased in the presence or absence of palmitate, indicating a more oxidized mitochondrial redox state. Palmitate significantly increased the 3-hydroxybutyrate/acetoacetate ratio in the presence of gluconeogenic and ureogenic substrates at all temperatures examined. The data suggest that provision of fatty acid has a protective effect in thermally stressed liver. Moreover, palmitate may substitute for the increased energy requirements of the hyperthermic state.