title: Bardoxolone Methyl Prevents High-Fat Diet-Induced Colon Inflammation in Mice.
abstract: Obesity induces chronic, low-grade inflammation, which increases the risk of colon cancer. We investigated the preventive effects of Bardoxolone methyl (BARD) on high-fat diet (HFD)-induced inflammation in a mouse colon. Male C57BL/6J mice (n=7) were fed a HFD (HFD group), HFD plus BARD (10 mg/kg) in drinking water (HFD/BARD group), or normal laboratory chow diet (LFD group) for 21 weeks. In HFD mice, BARD reduced colon thickness and decreased colon weight per length. This was associated with an increase in colon crypt depth and the number of goblet cells per crypt. BARD reduced the expression of F4/80 and CD11c but increased CD206 and IL-10, indicating an anti-inflammatory effect. BARD prevented an increase of the intracellular pro-inflammatory biomarkers (NF-қB, p NF-қB, IL-6, TNF-α) and cell proliferation markers (Cox2 and Ki67). BARD prevented fat deposition in the colon wall and prevented microbial population changes. Overall, we report the preventive effects of BARD on colon inflammation in HFD-fed mice through its regulation of macrophages, NF-қB, cytokines, Cox2 and Ki67, fat deposition and microflora.
authors.affiliation: Centre for Translational Neuroscience, School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW, Australia (CHLD, YY, AS, QZ, XH)
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, Australia (CHLD, YY, AS, QZ, XH)
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, Australia (CHLD, YY, AS, QZ, XH)|ANSTO LifeSciences, Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW, Australia (AS)
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, Australia (CHLD, YY, AS, QZ, XH)
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: XuZhou Medical College, Jiangsu Province 221004, The People's Republic of China (PZ)
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Centre for Translational Neuroscience, School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW, Australia (CHLD, YY, AS, QZ, XH)
authors.forename: Xu-Feng
authors.initials: XF
authors.lastname: Huang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003106:Colon / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D059305:Diet, High-Fat / Q000009:adverse effects*; D007249:Inflammation / Q000209:etiology* / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D009828:Oleanolic Acid; C445068:bardoxolone methyl
keywords: Bardoxolone methyl; Colon; High-fat diet; Inflammation