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.
Cohen
Paul
P
Laboratory of Molecular Genetics, Center for Studies in Physics and Biology, Rogosin Institute, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Miyazaki
Makoto
M
Socci
Nicholas D
ND
Hagge-Greenberg
Aaron
A
Liedtke
Wolfgang
W
Soukas
Alexander A
AA
Sharma
Ratnendra
R
Hudgins
Lisa C
LC
Ntambi
James M
JM
Friedman
Jeffrey M
JM
D000818:Animals; D001835:Body Weight; D003433:Crosses, Genetic; D015536:Down-Regulation; D004435:Eating; D004734:Energy Metabolism; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D020738:Leptin / Q000235:genetics / Q000502:physiology*; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008820:Mice, Obese; D008862:Microsomes, Liver / Q000201:enzymology; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010101:Oxygen Consumption; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism*; D014617:Vacuoles / Q000737:chemistry / Q000648:ultrastructure; D015431:Weight Loss
D020738:Leptin; D008055:Lipids; D008079:Lipoproteins, VLDL; D012333:RNA, Messenger; D013230:Stearoyl-CoA Desaturase