Hepatic triglyceride hydrolysis and development of ketogenesis in rabbits

Abstract

Ketogenesis from endogenous fatty acids or exogenous oleate plus carnitine has been studied in isolated hepatocytes from fetal, newborn, and 70-day-old rabbits. During the first 48 h after birth, hepatic triacylglycerol stores decrease by 80%. The hydrolysis of hepatic triacylglycerol stores has been studied in isolated hepatocytes from 24-h-old fasting rabbits by using lysosomal acid lipase inhibitors and lysosomotropic agents. Their addition decreases the rates of ketone body production by 60-70%, suggesting that hepatic triacylglycerol hydrolysis proceeds via an acid lipase located in the lysosomes. Whereas the rates of ketogenesis from endogenous or exogenous fatty acids are very low in isolated hepatocytes from fetal rabbit, an eightfold increase in the rate of ketogenesis occurs between 6 and 24 h after birth; furthermore the hydrolysis of triacylglycerol stores is sufficient to support the ketogenic capacity in the hepatocytes isolated from 24-h-old rabbits. The emergence of ketogenesis in newborn rabbit hepatocytes is triggered by birth-associated factors rather than to an accurate stage of fetal maturation. Fatty acids are mainly oxidized in the mitochondria because peroxisomal oxidation does not exceed 10-15% of the overall beta-oxidation. Isolated hepatocytes incubated with [1-14C]oleate exhibit at birth a preferential channeling of fatty acid into esterification (93% of oleate metabolized) rather than into oxidation. Conversely oleate oxidation represents 50% of total oleate metabolized 24 h after birth. Factors involved in this switch on of the partition of oleate into esterification and oxidation during the 1st day after birth are discussed.