Stimulation of hepatic triglyceride synthesis and secretion by clofibrate

Isolated hepatocytes prepared from rat and squirrel monkey livers were used to explore the mechanism of action of clofibrate, a hypolipidemic agent in current use. Addition of sodium clofibrate to cells suspended in Hanks medium stimulated the conversion of [1-¹⁴C]palmitate into esterified lipids and to ¹⁴CO₂. This agent also promoted the incorporation of [2-³H]glycerol into cellular lipids when fatty acids were present in the incubation medium. Triglycerides were the major lipid class increased by the drug. Sodium clofibrate enhanced the discharge of labeled lipids into the medium from liver cells prelabeled with [2-³H]glycerol. These data suggest that clofibrate does not lower plasma triglyceride levels by interference with hepatic triglyceride production or secretion.