4.7 Article

Ganoderic Acid A improves high fat diet-induced obesity, lipid accumulation and insulin sensitivity through regulating SREBP pathway

Journal

CHEMICO-BIOLOGICAL INTERACTIONS
Volume 290, Issue -, Pages 77-87

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2018.05.014

Keywords

Ganoderic Acid A; SREBPs; Obesity; Insulin resistance; Lipid accumulation

Funding

  1. Hangzhou Science and Technology Program [20160533B13]
  2. Population Planning Research Program of Zhejiang Province [2014KYA237]
  3. Program of Zhejiang University of traditional Chinese Medicine [2018ZY24]
  4. Science and Technology Development Program of Nanjing Medical University [2017NJMU086]

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Obesity and its major co-morbidity, type 2 diabetes, have been an alarming epidemic prevalence without an effective treatment available. Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acid and triglyceride. Therefore, inhibition of SREBP pathway may be a useful strategy to treat obesity with type 2 diabetes. Here, we identify a small molecule, Ganoderic Acid A (GAA), inhibits the SREBP expression and decreases the cellular levels of cholesterol and fatty acid in vitro. GAA also ameliorates body weight gain and fat accumulation in liver or adipose tissues, and improves serum lipid levels and insulin sensitivity in high fat diet (HFD)-induced obese mice. Consistently, GAA regulates SREBPs target genes and metabolism associated genes in liver or adipose tissues, which may directly contribute to the lower lipid level and improvement of insulin resistance. Taken together, GAA could be a potential leading compound for development of drugs for the prevention of obesity and insulin resistance.

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