Andrographolide Prevents High-Fat Diet-Induced Obesity in C57BL/6 Mice by Suppressing the Sterol Regulatory Element-Binding Protein Pathway

被引:61
作者
Ding, Lili [1 ,2 ,3 ]
Li, Jinmei [1 ,2 ,3 ,6 ]
Song, Baoliang [4 ]
Xiao, Xu [4 ]
Huang, Wendong [5 ]
Zhang, Binfeng [1 ,2 ,3 ]
Tang, Xiaowen [1 ,2 ,3 ]
Qi, Meng [1 ,2 ,3 ]
Yang, Qiming [1 ,2 ,3 ]
Yang, Qiaoling [1 ,2 ,3 ]
Yang, Li [1 ,2 ,3 ]
Wang, Zhengtao [1 ,2 ,3 ]
机构
[1] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, Shanghai Key Lab Complex Prescript, Shanghai 201203, Peoples R China
[2] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, MOE Key Lab Standardizat Chinese Med, Shanghai 201203, Peoples R China
[3] Shanghai R&D Ctr Standardizat Tradit Chinese Med, Shanghai, Peoples R China
[4] Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, State Key Lab Mol Biol, Shanghai, Peoples R China
[5] City Hope Natl Med Ctr, Beckman Res Inst, Dept Diabet & Metab Dis Res, Duarte, CA 91010 USA
[6] China Pharmaceut Univ, Dept Pharmacognosy, Nanjing, Jiangsu, Peoples R China
基金
中国博士后科学基金; 中国国家自然科学基金;
关键词
RECEPTOR LXR-ALPHA; METABOLIC SYNDROME; X-RECEPTOR; ADIPOCYTE DIFFERENTIATION; STATIN INTOLERANCE; ACID-METABOLISM; GENE-EXPRESSION; LDL RECEPTOR; CHOLESTEROL; LIVER;
D O I
10.1124/jpet.114.217968
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acids, and triglycerides. We investigated the effect of the specific SREBP suppressor andrographolide, a natural compound isolated from Andrographis paniculata, on the regulation of SREBP signaling by use of Western blot, reporter gene assay, and quantitative real-time polymerase chain reaction analysis. In addition, the antiobesity effects of andrographolide were evaluated in C57BL/6 mice with high-fat diet (HFD)-induced obesity. Our results showed that andrographolide downregulated the expressions of SREBPs target genes and decreased cellular lipid accumulation in vitro. Further, andrographolide (100 mg/kg per day) attenuated HFD-induced body weight gain and fat accumulation in liver or adipose tissues, and improved serum lipid levels and insulin or glucose sensitivity in HFD-induced obese mice. Andrographolide effectively suppressed the respiratory quotient, energy expenditure, and oxygen consumption, which may have contributed to the decreased body-weight gain of the obese mice fed with a HFD. Consistently, andrographolide regulated SREBP target genes and metabolism-associated genes in liver or brown adipose tissue, which may have directly contributed to the lower lipid levels and enhanced insulin sensitivity. Taken together, our results indicated that andrographolide ameliorated lipid metabolism and improved glucose use in mice with HFD-induced obesity. Andrographolide has potential as a leading compound in the prevention or treatment of obesity and insulin resistance.
引用
收藏
页码:474 / 483
页数:10
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