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Response gene to complement 32 deficiency protects against high‐fat diet‐induced insulin resistance and obesity with decreased hepatic lipogenesis in mice (767.7)
Author(s) -
Cui Xiaobing,
Chen Shiyou
Publication year - 2014
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.28.1_supplement.767.7
Subject(s) - lipogenesis , medicine , endocrinology , insulin resistance , sterol regulatory element binding protein , insulin , biology , cholesterol , chemistry , lipid metabolism , sterol
The objective of this study was to determine the effects of response gene to complement 32 (RGC‐32) on the development of obesity and insulin resistance in mice. Mice with RGC‐32 deficiency (RGC32‐/‐) gained less body weight with reduced epididymal fat and liver weight compared to the wild‐type animals after a 12‐week high‐fat diet. Biochemical analysis of blood, as well as glucose and insulin tolerance tests showed that RGC32‐/‐ improved insulin sensitivity and lowered serum triacylglycerol and low‐density lipoprotein/very‐low‐density lipoprotein cholesterol concentration. Hepatic lipid accumulation was also decreased in RGC32‐/‐ mice. Additional analysis revealed that lipogenic genes sterol regulatory element (SRE) binding protein (SREBP)‐1c, fatty acid synthase, and stearoyl‐CoA desaturase‐1 (SCD1) were decreased in the livers of RGC32‐/‐ mice. Mechanistic studies using mouse primary hepatocytes showed that SCD1 regulation by RGC‐32 was SREBP‐1c‐dependent since deletion or mutation of SRE abrogated SCD1 promoter activity mediated by RGC‐32. These data demonstrate that RGC‐32 induces SREBP‐1c‐dependent hepatic lipogenesis, which is essential for the high‐fat diet‐induced obesity and insulin resistance.