title: Bardoxolone Methyl Prevents Mesenteric Fat Deposition and Inflammation in High-Fat Diet Mice.
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.affiliation: Centre for Translational Neuroscience, School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.
authors.forename: Chi H L
authors.initials: CH
authors.lastname: Dinh
authors.affiliation: Centre for Translational Neuroscience, School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia ; ANSTO LifeSciences, Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW 2234, Australia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Szabo
authors.affiliation: Centre for Translational Neuroscience, School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Centre for Translational Neuroscience, School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.
authors.forename: Danielle
authors.initials: D
authors.lastname: Camer
authors.affiliation: Centre for Translational Neuroscience, School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.
authors.forename: Hongqin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Centre for Translational Neuroscience, School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.
authors.forename: Xu-Feng
authors.initials: XF
authors.lastname: Huang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004734:Energy Metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy; D050152:Intra-Abdominal Fat / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007473:Ion Channels / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000517:prevention & control*; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress; D047495:PPAR gamma / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: D016207:Cytokines; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047495:PPAR gamma; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D009828:Oleanolic Acid; C445068:bardoxolone methyl; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D055372:AMP-Activated Protein Kinases