Effects of short-term leptin exposure on triglyceride deposition in rat liver

Leptin has recently been suggested to play a role in the pathogenesis of he patic steatosis. Consequently, this study was designed to examine the direc t effects of portal leptin on the intrahepatic lipid contents in the postab sorptive state. Rat livers (n = 6 per group) were perfused in a recirculati ng system and portally infused with leptin (0.5 nmol/L, 5 nmol/L, and 25 nm ol/L), insulin (10 nmol/L), leptin (5 nmol/L) plus insulin (10 nmol/L), glu cagon (1 nmol/L), or vehicle (control). Intrahepatic contents of triglyceri des, free cholesterol, cholesteryl esters, and free fatty acids were determ ined from the lipid extract of frozen livers by capillary gas chromatograph y. Short-term leptin infusion increased total triglycerides in a concentrat ion-dependent (0.5 nmol/L: 2.8 +/- 0.4 mg/g, 5 nmol/L: 7.0 +/- 0.5 mg/g, 25 nmol/L: 8.3 +/- 1.0 mg/g) and time-dependent manner. Total triglycerides a lso rose during exposure to insulin plus leptin (7.2 +/- 0.6 mg/g) but fell during glucagon infusion (2.6 +/- 0.2 mg/g; control: 4.3 +/- 0.3 mg/g; P < .05). Leptin, insulin, and glucagon increased intrahepatic free cholestero l (P < .05). Free fatty acids were also higher during leptin exposure (0.5 nmol/L: 1.28 +/- 0.08 mg/g, 5 nmol/L: 0.47 +/- 0.01 mg/g, 25 nmol/L: 0.48 /- 0.04 mg/g, control: 0.38 +/- 0.03 mg/g; P < .05), In conclusion, hyperle ptinemia increases hepatic triglyceride content and may therefore contribut e to hepatic steatosis in hyperleptinemic obese patients.