Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss.
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.
Duke Scholars
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Related Subject Headings
- Weight Loss
- Vacuoles
- Stearoyl-CoA Desaturase
- RNA, Messenger
- Oxygen Consumption
- Oligonucleotide Array Sequence Analysis
- Mutation
- Microsomes, Liver
- Mice, Obese
- Mice
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Weight Loss
- Vacuoles
- Stearoyl-CoA Desaturase
- RNA, Messenger
- Oxygen Consumption
- Oligonucleotide Array Sequence Analysis
- Mutation
- Microsomes, Liver
- Mice, Obese
- Mice