Hepatic fatty acid metabolism in pigs and rats: major differences in endproducts, O2 uptake, and beta-oxidation.

Abstract

Models of mammalian hepatic lipid metabolism are based largely on observations made in adult rats, emphasizing ketogenesis as a primary adjunct to mitochondrial beta-oxidation. Studies using piglets have illustrated the divergent nature of intermediary metabolism in this model, wherein ketogenesis and beta-oxidation are small and acetogenesis is an important route of fuel carbon flux. To clarify potential species differences in hepatic lipid metabolism and its control, we compared O2 consumption and metabolic end products in fasted pig and rat liver homogenates treated with 1-[14C]C16:0. Carboxyl carbon accumulation in acid-soluble products (ASP) plus CO2 was threefold greater and O2 consumption was twofold greater in rats (P < 0.05). Unlike rats, pigs showed negligible carboxyl carbon accumulation in ketone bodies (3-7% of ASP), whereas acetate was a carboxyl carbon reservoir in both animals (17-31% of ASP in pigs). Malonate increased (approximately 2-fold) and antimycin/rotenone decreased (40-60%) radiolabel accumulation in acetate. These data concur with the hypotheses that comparatively low hepatic beta-oxidative flux in piglets is partially related to a smaller metabolic rate and that substantial acetogenesis occurs intramitochondrially in both pigs and rats.