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Bardoxolone methyl prevents obesity and hypothalamic dysfunction

Journal Article


Abstract


  • High-fat (HF) diet-induced obesity is associated with hypothalamic leptin resistance and low grade chronic inflammation, which largely impairs the neuroregulation of negative energy balance. Neuroregulation of negative energy balance is largely controlled by the mediobasal and paraventricular nuclei regions of the hypothalamus via leptin signal transduction. Recently, a derivative of oleanolic acid, bardoxolone methyl (BM), has been shown to have anti-inflammatory effects. We tested the hypothesis that BM would prevent HF diet-induced obesity, hypothalamic leptin resistance, and inflammation in mice fed a HF diet. Oral administration of BM via drinking water (10 mg/kg daily) for 21 weeks significantly prevented an increase in body weight, energy intake, hyperleptinemia, and peripheral fat accumulation in mice fed a HF diet. Furthermore, BM treatment prevented HF diet-induced decreases in the anorexigenic effects of peripheral leptin administration. In the mediobasal and paraventricular nuclei regions of the hypothalamus, BM administration prevented HF diet-induced impairments of the downstream protein kinase b (Akt) pathway of hypothalamic leptin signalling. BM treatment also prevented an increase in inflammatory cytokines, tumour necrosis factor alpha (TNFα) and interleukin 6 (IL-6) in these two hypothalamic regions. These results identify a potential novel neuropharmacological application for BM in preventing HF diet-induced obesity, hypothalamic leptin resistance, and inflammation.

Authors


  •   Camer, Danielle (external author)
  •   Yu, Yinghua
  •   Szabo, Alexander M. (external author)
  •   Wang, Hongqin
  •   Dinh, Chi H. L. (external author)
  •   Huang, Xu-Feng

Publication Date


  • 2016

Citation


  • Camer, D., Yu, Y., Szabo, A., Wang, H., Dinh, C. H. L. & Huang, X. (2016). Bardoxolone methyl prevents obesity and hypothalamic dysfunction. Chemico-Biological Interactions, 256 178-187.

Scopus Eid


  • 2-s2.0-84978254131

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/873

Number Of Pages


  • 9

Start Page


  • 178

End Page


  • 187

Volume


  • 256

Place Of Publication


  • Ireland

Abstract


  • High-fat (HF) diet-induced obesity is associated with hypothalamic leptin resistance and low grade chronic inflammation, which largely impairs the neuroregulation of negative energy balance. Neuroregulation of negative energy balance is largely controlled by the mediobasal and paraventricular nuclei regions of the hypothalamus via leptin signal transduction. Recently, a derivative of oleanolic acid, bardoxolone methyl (BM), has been shown to have anti-inflammatory effects. We tested the hypothesis that BM would prevent HF diet-induced obesity, hypothalamic leptin resistance, and inflammation in mice fed a HF diet. Oral administration of BM via drinking water (10 mg/kg daily) for 21 weeks significantly prevented an increase in body weight, energy intake, hyperleptinemia, and peripheral fat accumulation in mice fed a HF diet. Furthermore, BM treatment prevented HF diet-induced decreases in the anorexigenic effects of peripheral leptin administration. In the mediobasal and paraventricular nuclei regions of the hypothalamus, BM administration prevented HF diet-induced impairments of the downstream protein kinase b (Akt) pathway of hypothalamic leptin signalling. BM treatment also prevented an increase in inflammatory cytokines, tumour necrosis factor alpha (TNFα) and interleukin 6 (IL-6) in these two hypothalamic regions. These results identify a potential novel neuropharmacological application for BM in preventing HF diet-induced obesity, hypothalamic leptin resistance, and inflammation.

Authors


  •   Camer, Danielle (external author)
  •   Yu, Yinghua
  •   Szabo, Alexander M. (external author)
  •   Wang, Hongqin
  •   Dinh, Chi H. L. (external author)
  •   Huang, Xu-Feng

Publication Date


  • 2016

Citation


  • Camer, D., Yu, Y., Szabo, A., Wang, H., Dinh, C. H. L. & Huang, X. (2016). Bardoxolone methyl prevents obesity and hypothalamic dysfunction. Chemico-Biological Interactions, 256 178-187.

Scopus Eid


  • 2-s2.0-84978254131

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/873

Number Of Pages


  • 9

Start Page


  • 178

End Page


  • 187

Volume


  • 256

Place Of Publication


  • Ireland