Inhibition of hepatic triglyceride formation by clofibrate

The effect of clofibrate (CPIB) on hepatic glycerolipid formation has been studied in vivo and in vitro in the rat. Feeding 0.25% CPIB in laboratory chow significantly reduced serum triglyceride levels by 6 hr and concomitantly decreased the rate of glycerol-(14)C incorporation into hepatic and seru...

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Bibliographic Details
Published in:The Journal of clinical investigation 1971-11, Vol.50 (11), p.2339-2346
Main Authors: Adams, L L, Webb, W W, Fallon, H J
Format: Article
Language:English
Subjects:
Animals
Carbon Isotopes
Chromatography, Thin Layer
Clofibrate - pharmacology
Depression, Chemical
Glycerides - biosynthesis
Glycerides - blood
Glycerol - blood
Glycerol - metabolism
In Vitro Techniques
Liver - analysis
Liver - anatomy & histology
Liver - metabolism
Male
Organ Size
Rats
Triglycerides - analysis
Triglycerides - biosynthesis
Triglycerides - blood
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Summary:The effect of clofibrate (CPIB) on hepatic glycerolipid formation has been studied in vivo and in vitro in the rat. Feeding 0.25% CPIB in laboratory chow significantly reduced serum triglyceride levels by 6 hr and concomitantly decreased the rate of glycerol-(14)C incorporation into hepatic and serum glycerides, in vivo. These changes persisted for at least 14 days. A similar decrease in serum triglyceride and glycerol incorporation into hepatic glycerides was observed in rats fed high glucose diets containing 0.25% CPIB. Serum glycerol was reduced by feeding CPIB for 14 days. The formation of diglyceride and triglyceride from (14)C-sn-glycerol-3-P by rat liver homogenates was inhibited by addition of 1-40 mM CPIB to the reaction mixture. These results suggest that CPIB reduces hepatic glycerolipid synthesis, possibly by inhibition of one or more reactions in the esterification of sn-glycerol-3-P. This change may account for the early fall in serum triglyceride. At later time periods, serum glycerol levels fall and in some experiments, hepatic triglyceride content increases. Therefore, it is likely that additional metabolic alterations may contribute to the sustained hypotriglyceridemic effects of CPIB.
ISSN:0021-9738
DOI:10.1172/JCI106732