Publication Date:
2002-07-13
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Paul -- Miyazaki, Makoto -- Socci, Nicholas D -- Hagge-Greenberg, Aaron -- Liedtke, Wolfgang -- Soukas, Alexander A -- Sharma, Ratnendra -- Hudgins, Lisa C -- Ntambi, James M -- Friedman, Jeffrey M -- GM07739/GM/NIGMS NIH HHS/ -- R01-DK41096/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2002 Jul 12;297(5579):240-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉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.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12114623" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Body Weight
;
Crosses, Genetic
;
Down-Regulation
;
Eating
;
Energy Metabolism
;
Female
;
Gene Expression
;
Gene Expression Profiling
;
Leptin/genetics/*physiology
;
Lipid Metabolism
;
Lipids/analysis
;
Lipoproteins, VLDL/metabolism
;
Liver/*enzymology/metabolism/ultrastructure
;
Male
;
Mice
;
Mice, Obese
;
Microsomes, Liver/enzymology
;
Mutation
;
Oligonucleotide Array Sequence Analysis
;
Oxygen Consumption
;
RNA, Messenger/genetics/metabolism
;
Stearoyl-CoA Desaturase/genetics/*metabolism
;
Vacuoles/chemistry/ultrastructure
;
*Weight Loss
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
