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

P Cohen, M Miyazaki, ND Socci, A Hagge-Greenberg… - Science, 2002 - science.org
P Cohen, M Miyazaki, ND Socci, A Hagge-Greenberg, W Liedtke, AA Soukas, R Sharma…
Science, 2002science.org
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 …
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.
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