Fluvastatin Sodium Ameliorates Obesity through Brown Fat Activation

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ID: 107802
2019
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Abstract
Brown adipose tissue (BAT), an organ that burns energy through uncoupling thermogenesis, is a promising therapeutic target for obesity. However, there are still no safe anti-obesity drugs that target BAT in the market. In the current study, we performed large scale screening of 636 compounds which were approved by Food and Drug Administration (FDA) to find drugs that could significantly increase uncoupling protein 1 (UCP1) mRNA expression by real-time PCR. Among those UCP1 activators, most of them were antibiotics or carcinogenic compounds. We paid particular attention to fluvastatin sodium (FS), because as an inhibitor of the cellular hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase, FS has already been approved for treatment of hypercholesteremia. We found that in the cellular levels, FS treatment significantly increased UCP1 expression and BAT activity in human brown adipocytes. Consistently, the expression of oxidative phosphorylation-related genes was significantly increased upon FS treatment without differences in adipogenic gene expression. Furthermore, FS treatment resisted to high-fat diet (HFD)-induced body weight gain by activating BAT in the mice model. In addition, administration of FS significantly increased energy expenditure, improved glucose homeostasis and ameliorated hepatic steatosis. Furthermore, we reveal that FS induced browning in subcutaneous white adipose tissue (sWAT) known to have a beneficial effect on energy metabolism. Taken together, our results clearly demonstrate that as an effective BAT activator, FS may have great potential for treatment of obesity and related metabolic disorders.
Reference Key
yin2019fluvastatininternational Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Yin, Na;Zhang, Hanlin;Ye, Rongcai;Dong, Meng;Lin, Jun;Zhou, Huiqiao;Huang, Yuanyuan;Chen, Li;Jiang, Xiaoxiao;Nagaoka, Kentaro;Zhang, Chuanhai;Jin, Wanzhu;
Journal International journal of molecular sciences
Year 2019
DOI
DOI not found
URL
https://www.mdpi.com/1422-0067/20/7/1622
Keywords
chemistry Organic Chemistry Biology (General) Other systems of medicine neoplasms. tumors. oncology. including cancer and carcinogens diseases of the endocrine glands. clinical endocrinology

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