Steroidogenic Acute Regulatory Protein (StAR) Overexpression Reduces Inflammation and Insulin Resistance in Obese Mice

• Published in: Journal of cellular biochemistry 2017-11, Vol.118 (11), p.3932-3942
• Main Authors: Qiu, Yanyan, Sui, Xianxian, Cao, Shengxuan, Li, Xiaobo, Ning, Yanxia, Wang, Songmei, Yin, Lianhua, Zhi, Xiuling
• Format: Article
• Language: English
• Subjects: Adipose tissue; Adipose Tissue - metabolism; Adipose Tissue - pathology; Animals; Cholesterol; Diabetes mellitus; Dietary Fats - adverse effects; Dietary Fats - pharmacology; Enzyme-linked immunosorbent assay; FATTY ACID; Fatty acids; Fatty Acids, Unsaturated - blood; Gas chromatography; Gene expression; Glucose tolerance; Hyperlipidemia; Hypertrophy; INFLAMMATION; Inflammatory response; Insulin; INSULIN RESISTANCE; Male; Mass spectrometry; Mass spectroscopy; Mice; Mitochondria; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Nitric Acid - blood; Nitric oxide; Obesity - chemically induced; Obesity - genetics; Obesity - metabolism; Obesity - pathology; Peroxisome proliferator-activated receptors; Phosphoproteins - biosynthesis; Phosphoproteins - genetics; PPAR gamma - genetics; PPAR gamma - metabolism; PPARγ; Proteins; Resistance factors; Risk analysis; Risk factors; Sensitivity analysis; Skeletal muscle; STEROIDOGENIC ACUTE REGULATORY PROTEIN; Western blotting
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.26046

ABSTRACT Steroidogenic acute regulatory protein (StAR), a mitochondrial cholesterol delivery protein, plays a beneficial role in hyperlipidemia, NAFLD, and endothelial inflammation. Elevated circulating fatty acids and low grade inflammation are known as key risk factors of insulin resistance and type 2 diabetes. In the present study, C57BL/6J mice were fed with HFD and infected with recombinant adenovirus expressing StAR by tail‐vein injection. Intraperitoneal glucose/insulin tolerance test was performed to assess the insulin sensitivity. Morphological analysis and intramuscular lipid determination were used to illustrate the adipose hypertrophy and ectopic fat accumulation in skeletal muscle. The levels of inflammatory factor and nitric oxide were determined by ELISA and classic Griess reagent methods, respectively. The fatty acids composition was analysis using gas chromatography‐mass spectrometry (GC‐MS). The expression of genes associated with inflammation and insulin resistance were determined by Western blotting and qPCR to elucidate the underlying mechanism. We demonstrated that StAR overexpression ameliorated insulin resistance and systemic inflammatory response with the reduction of adipose hypertrophy and intramuscular lipid in HFD‐fed mice. In addition, StAR overexpression increased serum unsaturated fatty acids (UFAs) and PPARγ expression in muscle and adipose tissue of obese mice. In conclusion, StAR may activate PPARγ by increasing UFAs, which leads to a protective role in systemic inflammation and insulin resistance in obese mice. J. Cell. Biochem. 118: 3932–3942, 2017. © 2017 Wiley Periodicals, Inc. StAR plays a beneficial role in obese mice during the onset of insulin resistance and type 2 diabetes. StAR may activate PPARγ by unsaturated fatty acids, which leads to a protective role of StAR in systemic inflammation and insulin resistance.