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

Science. 2002 Jul 12;297(5579):240-3. doi: 10.1126/science.1071527.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Body Weight
  • Crosses, Genetic
  • Down-Regulation
  • Eating
  • Energy Metabolism
  • Female
  • Gene Expression
  • Gene Expression Profiling
  • Leptin / genetics
  • Leptin / physiology*
  • Lipid Metabolism
  • Lipids / analysis
  • Lipoproteins, VLDL / metabolism
  • Liver / enzymology*
  • Liver / metabolism
  • Liver / ultrastructure
  • Male
  • Mice
  • Mice, Obese
  • Microsomes, Liver / enzymology
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Oxygen Consumption
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Stearoyl-CoA Desaturase / genetics
  • Stearoyl-CoA Desaturase / metabolism*
  • Vacuoles / chemistry
  • Vacuoles / ultrastructure
  • Weight Loss*


  • Leptin
  • Lipids
  • Lipoproteins, VLDL
  • RNA, Messenger
  • Stearoyl-CoA Desaturase