17-DMAG, an Hsp90 inhibitor, ameliorates ovariectomy-induced obesity in rats

doi:10.1016/j.lfs.2019.116672

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標題:	17-DMAG, an Hsp90 inhibitor, ameliorates ovariectomy-induced obesity in rats
作者:	Yung-Chieh Tsai(蔡永杰) Leu, Sy-Ying Chen, Shu-Ying Kung, Ching-Wen Lee, Yen-Mei Liu, Yia-Ping Yen, Mao-Hsiung Cheng, Pao-Yun
貢獻者:	Chi Mei Med Ctr, Dept Obstet & Gynecol Taipei Med Univ, Dept Med Chia Nan Univ Pharm & Sci, Dept Sport Management Natl Def Med Ctr, Grad Inst Physiol, Dept Physiol & Biophys HungKung Univ, Dept Nursing Tzu Chi Univ Sci & Technol, Dept Nursing Natl Def Med Ctr, Dept Pharmacol Cheng Hsin Gen Hosp, Dept Psychiat Natl Def Med Ctr, Sch Med, Triserv Gen Hosp, Dept Psychiat
關鍵字:	17-DMAG Obesity Autophagy Hsp70 Ovariectomy
日期:	2019
上傳時間:	2020-07-29 13:47:01 (UTC+8)
出版者:	PERGAMON-ELSEVIER SCIENCE LTD
摘要:	Aims: Obesity is not only associated with metabolic diseases but is also a symptom of menopause in women. To date, there are no effective drugs for the management of obesity, and it is important to find new agents with fewer side effects, for the treatment of obesity. This study aimed to determine the anti-obesity effect of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a heat shock protein 90 (Hsp90) inhibitor, and its underlying mechanism in rats with ovariectomy-induced obesity. Main methods: Ovariectomy (Ovx) rats were treated with 17-DMAG (1 mg kg(-1), intraperitoneally) for eight weeks from one week after surgery. The body weight, food intake, locomotor activity, adipogenic- and autophagy-related protein expression in white adipose tissue (WAT) and plasma triglyceride (TG) levels were measured in sham and Ovx rats. Key findings: Compared with sham rats, Ovx rats showed increased weight gain, food intake, WAT mass, TG levels, adipogenic protein expression, and decreased locomotor activity. Furthermore, autophagy-related proteins and Foxo3a of WAT were significantly increased in Ovx rats. However, with the exclusion of increased food intake, the changes induced by Ovx were all reversed in 17-DMAG-treated Ovx rats. In addition, the expression of Hsp70 and phosphorylation of Akt increased in 17-DMAG-treated Ovx rats. Significance: These results suggest that 17-DMAG significantly ameliorated obesity induced by Ovx, and this phenomenon is accompanied by the downregulation of adipogenic-related and autophagy-related proteins as well as the upregulation of Akt-phosphorylation and Hsp70 expression. Therefore, 17-DMAG may be a potential agent for preventing or treating obesity in postmenopausal women.
關聯:	Life Sciences, v.232, 1 September 2019, 116672
显示于类别:	[運動管理系] 期刊論文

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