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

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 ty...

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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
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container_title Journal of cellular biochemistry
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Sui, Xianxian
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description 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.
doi_str_mv 10.1002/jcb.26046
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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. 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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.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28402022</pmid><doi>10.1002/jcb.26046</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-8248-4090</orcidid></addata></record>
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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
title Steroidogenic Acute Regulatory Protein (StAR) Overexpression Reduces Inflammation and Insulin Resistance in Obese Mice
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