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Bardoxolone methyl prevents mesenteric fat deposition and inflammation in high-fat diet mice

Journal Article


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Abstract


  • Mesenteric fat belongs to visceral fat. An increased deposition of mesenteric fat contributes to obesity associated complications such as type 2 diabetes and cardiovascular diseases. We have investigated the therapeutic effects of bardoxolone methyl (BARD) on mesenteric adipose tissue of mice fed a high-fat diet (HFD). Male C57BL/6J mice were administered oral BARD during HFD feeding (HFD/BARD), only fed a high-fat diet (HFD), or fed low-fat diet (LFD) for 21 weeks. Histology and immunohistochemistry were used to analyse mesenteric morphology and macrophages, while Western blot was used to assess the expression of inflammatory, oxidative stress, and energy expenditure proteins. Supplementation of drinking water with BARD prevented mesenteric fat deposition, as determined by a reduction in large adipocytes. BARD prevented inflammation as there were fewer inflammatory macrophages and reduced proinflammatory cytokines (interleukin-1 beta and tumour necrosis factor alpha). BARD reduced the activation of extracellular signal-regulated kinase (ERK) and Akt, suggesting an antioxidative stress effect. BARD upregulates energy expenditure proteins, judged by the increased activity of tyrosine hydroxylase (TH) and AMP-activated protein kinase (AMPK) and increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and uncoupling protein 2 (UCP2) proteins. Overall, BARD induces preventive effect in HFD mice through regulation of mesenteric adipose tissue.

Authors


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

Publication Date


  • 2015

Citation


  • Dinh, C. H. L., Szabo, A. M., Yu, Y., Camer, D., Wang, H. & Huang, X. (2015). Bardoxolone methyl prevents mesenteric fat deposition and inflammation in high-fat diet mice. The Scientific World Journal, 2015 549352-1-549352-15.

Scopus Eid


  • 2-s2.0-84947460040

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1590&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/568

Has Global Citation Frequency


Start Page


  • 549352-1

End Page


  • 549352-15

Volume


  • 2015

Place Of Publication


  • United States

Abstract


  • Mesenteric fat belongs to visceral fat. An increased deposition of mesenteric fat contributes to obesity associated complications such as type 2 diabetes and cardiovascular diseases. We have investigated the therapeutic effects of bardoxolone methyl (BARD) on mesenteric adipose tissue of mice fed a high-fat diet (HFD). Male C57BL/6J mice were administered oral BARD during HFD feeding (HFD/BARD), only fed a high-fat diet (HFD), or fed low-fat diet (LFD) for 21 weeks. Histology and immunohistochemistry were used to analyse mesenteric morphology and macrophages, while Western blot was used to assess the expression of inflammatory, oxidative stress, and energy expenditure proteins. Supplementation of drinking water with BARD prevented mesenteric fat deposition, as determined by a reduction in large adipocytes. BARD prevented inflammation as there were fewer inflammatory macrophages and reduced proinflammatory cytokines (interleukin-1 beta and tumour necrosis factor alpha). BARD reduced the activation of extracellular signal-regulated kinase (ERK) and Akt, suggesting an antioxidative stress effect. BARD upregulates energy expenditure proteins, judged by the increased activity of tyrosine hydroxylase (TH) and AMP-activated protein kinase (AMPK) and increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and uncoupling protein 2 (UCP2) proteins. Overall, BARD induces preventive effect in HFD mice through regulation of mesenteric adipose tissue.

Authors


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

Publication Date


  • 2015

Citation


  • Dinh, C. H. L., Szabo, A. M., Yu, Y., Camer, D., Wang, H. & Huang, X. (2015). Bardoxolone methyl prevents mesenteric fat deposition and inflammation in high-fat diet mice. The Scientific World Journal, 2015 549352-1-549352-15.

Scopus Eid


  • 2-s2.0-84947460040

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1590&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/568

Has Global Citation Frequency


Start Page


  • 549352-1

End Page


  • 549352-15

Volume


  • 2015

Place Of Publication


  • United States