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Hepatic Stearoyl‐CoA Desaturase‐1 expression is required for Carbohydrate‐Induced Adiposity and Hepatic Steatosis
Author(s) -
Ntambi James Mukasa,
Flowers Matthew T.,
Sampath Harini,
Chu Kiki,
Liu Xueqing,
Miyazaki Makoto
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.116.1
Subject(s) - lipogenesis , steatosis , medicine , endocrinology , insulin resistance , carbohydrate responsive element binding protein , triglyceride , fatty liver , lipid metabolism , carbohydrate metabolism , biology , obesity , cholesterol , biochemistry , gene , disease , transcription factor
Stearoyl‐CoA desaturase is a delta‐9 desaturase that catalyzes the desaturation of saturated fatty acids into monounsaturated fatty acids, which serve as the preferred substrates for synthesis of numerous tissue lipids. It is also a critical regulator of energy metabolism and its expression is implicated in numerous human diseases that include obesity, non‐insulin‐dependent diabetes, hypertension, cardiovascular disease and immune disorders. We investigated the role of SCD1 in liver metabolism by generating mice with a liver‐specific knockout of Scd1 (LKO) using Cre‐lox technology. We found that unlike global SCD1 KO (GKO) mice, LKO mice fed high‐fat diet were not protected against obesity, hepatic steatosis, and whole‐body insulin resistance. On the other hand, LKO mice were protected from high‐carbohydrate diet‐induced adiposity and hepatic steatosis similar to GKO mice. The LKO mice displayed a marked decrease in the rate of lipogenesis with decreased expression of the nuclear contents of SREBP‐1 and ChREBP and their target genes. Oleate but not stearate supplementation to the high carbohydrate diet normalized adiposity, triglyceride secretion and hepatic lipogenesis of LKO mice. These results indicate that hepatic SCD1 expression, and thus oleate is required for carbohydrate‐induced adiposity and lipogenesis but loss of SCD1 activity in extra hepatic tissues is required to protect mice from high‐fat diet‐induced obesity and insulin resistance. Supported by NIH grant DK 62388.