Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Cohen, P; Miyazaki, M; Socci, ND; Hagge-Greenberg, A; Liedtke, W; Soukas, AA; Sharma, R; Hudgins, LC; Ntambi, JM; Friedman, JM

Published Date

  • July 12, 2002

Published In

Volume / Issue

  • 297 / 5579

Start / End Page

  • 240 - 243

PubMed ID

  • 12114623

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.1071527

Language

  • eng

Conference Location

  • United States