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

Yung-Chieh Tsai1, Sy-Ying Leu2, Shu-Ying Chen3

  • 1Department of Obstetrics and Gynecology, Chi-Mei Medical Center, Tainan, Taiwan; Department of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Sport Management, Chia Nan University of Pharmacy and Science, 71710 Tainan, Taiwan.

Life Sciences
|July 24, 2019
PubMed
Abstract

Insights

17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) reversed obesity in ovariectomy-induced rats by downregulating adipogenic and autophagy proteins. This heat shock protein 90 (Hsp90) inhibitor shows potential for treating postmenopausal obesity.

Area of Science:

  • Endocrinology and Metabolism
  • Molecular Biology

Background:

  • Obesity is a growing health concern, often linked to metabolic disorders and menopausal changes in women.
  • Current obesity treatments lack efficacy and often have significant side effects, necessitating the development of novel therapeutic agents.

Purpose of the Study:

  • To investigate the anti-obesity effects of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a heat shock protein 90 (Hsp90) inhibitor.
  • To elucidate the underlying mechanisms of 17-DMAG's action in a rat model of ovariectomy-induced obesity.

Main Methods:

  • Ovariectomy (Ovx) was performed on rats to induce obesity.
  • Rats were treated with 17-DMAG (1 mg/kg) intraperitoneally for eight weeks.
  • Key parameters measured included body weight, food intake, locomotor activity, white adipose tissue (WAT) protein expression (adipogenic and autophagy markers), and plasma triglyceride (TG) levels.

Main Results:

  • Ovx rats exhibited increased weight gain, food intake, WAT mass, TG levels, and adipogenic protein expression, alongside decreased locomotor activity.
  • 17-DMAG treatment reversed most Ovx-induced changes, except for increased food intake.
  • 17-DMAG administration led to increased expression of Hsp70 and Akt phosphorylation in Ovx rats.

Conclusions:

  • 17-DMAG effectively ameliorated obesity in ovariectomy-induced rats.
  • The anti-obesity effect is associated with the downregulation of adipogenic and autophagy-related proteins and upregulation of Akt phosphorylation and Hsp70.
  • 17-DMAG presents a potential therapeutic strategy for obesity in postmenopausal women.
Keywords:
17-DMAGAutophagyHsp70ObesityOvariectomy

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