Development and regulation of ketogenesis in hepatocytes isolated from newborn rats

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Abstract
The development of fatty acid metabolism was studied in isolated hepatocytes from newborn rats. Ketone body production from oleate is increased 6-fold between 0-16 h after birth. This increase is related to an enhanced .BETA.-oxidation rather than to a channeling of acetyl-CoA from the tricarboxylic acid cycle to ketone body synthesis. The increase in oleate oxidation is not related to a decreased esterification rate, as the latter is already low at birth and does not decrease further. At birth, lipogenic rate is 2- to 3-fold lower than in fed adult rats and it decreases to undetectable values in 16 h-old rats. A 90% inhibition of lipogenesis in hepatocytes of newborn rats (O h) by glucagon and 5-(tetradecyloxy)-2-furoic acid does not lead to an increased oxidation of nonesterified fatty acids. The inverse relationship between lipogenesis and ketogenesis in the starved newborn rat is probably not responsible for the switch-on of fatty acid oxidation at birth, Moreover, ketogenesis from octanoate, a medium-chain fatty acid, the oxidation of which is independent of carnitine acyltransferase, follows the same developmental pattern at birth as that from oleate.