Hepatic triglyceride lipases—Effect of clofibrate and halofenate

Abstract

Liver lipases could be important for regulating hepatic intracellular triglyceride (TG) concentration and, thus, TG secretion. The possibility that the hypotriglyceridemic drugs clofibrate (CPIB) and halofenate (HFA) reduce hepatic net TG synthesis by stimulating hepatic lipases has been investigated in control and orotic acid fed rats. Liver lipase activities were measured at pH 5, 7.5 and 8.5 in liver homogenates from control and drug-treated animals. The acid lipase was particularly sensitive to changes in hepatic TG concentration, increasing when hepatic TG levels were increased by feeding orotic acid and decreasing after treatment with either HFA of CPIB, drugs which lower hepatic TG levels. Both CPIB and HFA prevented the fatty liver produced by orotic acid. Neither drug increased the activity of the hepatic lipases with triolein as substrate (at an enzyme-saturating concentration) and, thus, the abilities of HFA and CPIB to decrease hepatic net TG synthesis and to prevent orotic acid-induced fatty liver are not related to effects on these liver lipases. Rather, they may be related to reducing the availability of fatty acids for de novo TG synthesis. CPIB and HFA produced a 65–75 per cent decrease in plasma free fatty acid (FFA) concentrations and this decrease could be important since circulating free fatty acids are a principal source of the fatty acid needed for hepatic TG synthesis.