RT Journal Article
SR Electronic
T1 Role for Stearoyl-CoA Desaturase-1 in Leptin-Mediated Weight Loss
JF Science
JO Science
FD American Association for the Advancement of Science
SP 240
OP 243
DO 10.1126/science.1071527
VO 297
IS 5579
A1 Cohen, Paul
A1 Miyazaki, Makoto
A1 Socci, Nicholas D.
A1 Hagge-Greenberg, Aaron
A1 Liedtke, Wolfgang
A1 Soukas, Alexander A.
A1 Sharma, Ratnendra
A1 Hudgins, Lisa C.
A1 Ntambi, James M.
A1 Friedman, Jeffrey M.
YR 2002
UL http://science.sciencemag.org/content/297/5579/240.abstract
AB Leptin elicits a metabolic response that cannot be explained by its anorectic effects alone. To examine the mechanism underlying leptin's metabolic actions, we used transcription profiling to identify leptin-regulated genes in ob/ob liver. Leptin was found to specifically repress RNA levels and enzymatic activity of hepatic stearoyl–CoA desaturase-1 (SCD-1), which catalyzes the biosynthesis of monounsaturated fatty acids. Mice lacking SCD-1 were lean and hypermetabolic. ob/ob mice with mutations in SCD-1 were significantly less obese than ob/ob controls and had markedly increased energy expenditure. ob/ob mice with mutations in SCD-1 had histologically normal livers with significantly reduced triglyceride storage and VLDL (very low density lipoprotein) production. These findings suggest that down-regulation of SCD-1 is an important component of leptin's metabolic actions.