Role for Stearoyl-CoA Desaturase-1 in Leptin-Mediated Weight Loss
Paul Cohen,1
Makoto Miyazaki,5
Nicholas D. Socci,12
Aaron Hagge-Greenberg,1
Wolfgang Liedtke,1
Alexander A. Soukas,1
Ratnendra Sharma,1
Lisa C. Hudgins,3
James M. Ntambi,56
Jeffrey M. Friedman14*
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.
1 Laboratory of Molecular Genetics,
2 Center for Studies in Physics and Biology,
3 Rogosin Institute,
4 Howard
Hughes Medical Institute, The Rockefeller University, 1230 York Avenue,
New York, NY 10021, USA.
5 Department of
Biochemistry and
6 Department of Nutritional
Sciences, University of Wisconsin, Madison, WI 53706, USA.
*
To whom correspondence should be addressed. E-mail:
friedj{at}rockvax.rockefeller.edu
