Regulation of ketogenesis during the suckling–weanling transition in the rat. Studies with isolated hepatocytes

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Abstract
The rates of ketogenesis from endogenous substrates, butyrate or oleate, were measured in isolated hepatocytes from suckling and weanling rats. Ketogenesis from endogenous substrate and from oleate decreased on weaning, whereas the rate from butyrate remained unchanged. The major site of regulation of ketogenesis during this period of development apparently involves the disposal of long-chain fatty acyl-CoA between the esterification and .beta.-oxidation pathways. Modulators of lipogenesis [dihydroxyacetone and 5-(tetradecyloxy)-2-furoic acid] did not alter the rate of ketogenesis in hepatocytes from suckling rats; this may be due to the low rate of lipogenesis in these cells. Hepatocytes from fed weanling rats have a high rate of lipogenesis and evidence is presented is for a reciprocal relationship between ketogenesis and lipogenesis, and ketogenesis and esterification in these cells. Dibutyryl cyclic(c)AMP stimulated ketogenesis from oleate in hepatocytes from fed weanling rats, even in the presence of an inhibitor of lipogenesis [5-(tetradecyloxy)-2-furoic acid], but not in cells from suckling rats. cAMP may act via inhibition of esterification. In hepatocytes from suckling rats ketogenesis is apparently already maximally stimulated by the high basal concentrations of cAMP.