Effect of glycerol and dihydroxyacetone on hepatic lipogenesis.
Glycerol is a dietary component which is metabolized primarily by the liver and kidney where it is used mainly for glucose synthesis. The metabolism of glycerol is very similar to that of dihydroxyacetone which can be considered its more oxidized counterpart. The effects of these substrates on hepatic lipogenesis and gluconeogenesis were examined. In isolated hepatocytes, 10 mM dihydroxyacetone caused a large increase in glucose output and stimulated lipogenesis without affecting the lactate/pyruvate ratio or the total ATP content of the cells. (As compared to dihydroxyacetone, 10 mM glycerol was less effective as a gluconeogenic substrate, increased the lactate/pyruvate ratio, caused a slight decrease in the total ATP content, and inhibited lipogenesis by at least 40% depending on the type of diet fed to the rats.) The fall in ATP levels was very small and did not correlate with the changes in fatty acid synthesis. The immediate cause of the inhibition of lipogenesis, brought about by glycerol in hepatocytes from sucrose fed rats, seemed to be a large decrease in pyruvate levels. This did not result from impairment of glycolysis but from a rise in the cytosolic NADH/NAD ratio.
Carmona
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A
Department of Physiological Sciences, School of Veterinary Medicine, University of California, Davis 95616.
Freedland
R A
RA
D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004098:Dihydroxyacetone / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D005990:Glycerol / Q000494:pharmacology*; D006885:Hydroxybutyrates / Q000378:metabolism; D007657:Ketone Bodies / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013223:Statistics as Topic; D013772:Tetramethylphenylenediamine / Q000494:pharmacology; D014306:Trioses / Q000494:pharmacology*
D000090:Acetoacetates; D004040:Dietary Carbohydrates; D006885:Hydroxybutyrates; D007657:Ketone Bodies; D007773:Lactates; D008055:Lipids; D011773:Pyruvates; D014306:Trioses; C016635:acetoacetic acid; D000255:Adenosine Triphosphate; D005947:Glucose; D004098:Dihydroxyacetone; D013772:Tetramethylphenylenediamine; D005990:Glycerol; D020155:3-Hydroxybutyric Acid