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 hepatic steatosis. Consequently, this study was designed to examine the direct effects of portal leptin on the intrahepatic lipid contents in the postabsorptive state. Rat livers (n = 6 per group) were perfused in a recirculating system and portally infused with leptin (0.5 nmol/L, 5 nmol/L, and 25 nmol/L), insulin (10 nmol/L), leptin (5 nmol/L) plus insulin (10 nmol/L), glucagon (1 nmol/L), or vehicle (control). Intrahepatic contents of triglycerides, free cholesterol, cholesteryl esters, and free fatty acids were determined from the lipid extract of frozen livers by capillary gas chromatography. Short-term leptin infusion increased total triglycerides in a concentration-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 also 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 cholesterol (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, hyperleptinemia increases hepatic triglyceride content and may therefore contribute to hepatic steatosis in hyperleptinemic obese patients.
Roden
M
M
Division of Endocrinology and Metabolism, Department of Internal Medicine III, Vienna, Austria. michael.roden@akh-wien.ac.at
Anderwald
C
C
Fürnsinn
C
C
Waldhäusl
W
W
Lohninger
A
A
D000818:Animals; D002331:Carnitine / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D007262:Infusions, Intravenous; D020738:Leptin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D011169:Portal Vein; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism*
D002788:Cholesterol Esters; D005230:Fatty Acids, Nonesterified; D020738:Leptin; D014280:Triglycerides; D002784:Cholesterol; D002331:Carnitine