Premium
Stearoyl‐CoA desaturase as a new drug target for obesity treatment
Author(s) -
Dobrzyn A.,
Ntambi J. M.
Publication year - 2005
Publication title -
obesity reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.845
H-Index - 162
eISSN - 1467-789X
pISSN - 1467-7881
DOI - 10.1111/j.1467-789x.2005.00177.x
Subject(s) - lipogenesis , steatosis , endocrinology , medicine , metabolic syndrome , fatty liver , leptin , obesity , stearoyl coa desaturase , beta oxidation , diabetes mellitus , insulin resistance , type 2 diabetes , lipid metabolism , chemistry , metabolism , biochemistry , disease , gene expression , gene
Summary Stearoyl‐CoA desaturase (SCD), the rate‐limiting enzyme in monounsaturated fatty acid synthesis, has recently been shown to be the critical control point regulating hepatic lipogenesis and lipid oxidation. As several manifestations of the metabolic syndrome and type 2 diabetes mellitus are associated with alterations in intracellular lipid partitioning, we propose that SCD1 may be a potential therapeutic target in the treatment of obesity and the metabolic syndrome. In support of this notion, we have shown that SCD1‐deficient mice have increased energy expenditure, reduced body adiposity, increased insulin sensitivity and are resistant to diet‐induced obesity and liver steatosis. Furthermore, SCD1 was found to be specifically repressed during leptin‐mediated weight loss, and leptin‐deficient ob/ob mice lacking SCD1 showed marked correction of the hypometabolic phenotype and hepatic steatosis. Much evidence indicates that the direct anti‐steatotic effect of SCD1 deficiency stems from increased fatty acid oxidation and decreased lipid synthesis. All of these findings reveal that pharmacological manipulation of SCD activity might be of benefit in the treatment of obesity, diabetes, liver steatosis and other diseases of the metabolic syndrome.