Bardoxolone Methyl Prevents Fat Deposition and Inflammation in Brown Adipose Tissue and Enhances Sympathetic Activity in Mice Fed a High-Fat Diet. 2015

Chi H L Dinh, and Alexander Szabo, and Yinghua Yu, and Danielle Camer, and Qingsheng Zhang, and Hongqin Wang, and Xu-Feng Huang
Centre for Translational Neuroscience, School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia. hlcd893@uowmail.edu.au.

Obesity results in changes in brown adipose tissue (BAT) morphology, leading to fat deposition, inflammation, and alterations in sympathetic nerve activity. Bardoxolone methyl (BARD) has been extensively studied for the treatment of chronic diseases. We present for the first time the effects of oral BARD treatment on BAT morphology and associated changes in the brainstem. Three groups (n = 7) of C57BL/6J mice were fed either a high-fat diet (HFD), a high-fat diet supplemented with BARD (HFD/BARD), or a low-fat diet (LFD) for 21 weeks. BARD was administered daily in drinking water. Interscapular BAT, and ventrolateral medulla (VLM) and dorsal vagal complex (DVC) in the brainstem, were collected for analysis by histology, immunohistochemistry and Western blot. BARD prevented fat deposition in BAT, demonstrated by the decreased accumulation of lipid droplets. When administered BARD, HFD mice had lower numbers of F4/80 and CD11c macrophages in the BAT with an increased proportion of CD206 macrophages, suggesting an anti-inflammatory effect. BARD increased phosphorylation of tyrosine hydroxylase in BAT and VLM. In the VLM, BARD increased energy expenditure proteins, including beta 3-adrenergic receptor (β3-AR) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Overall, oral BARD prevented fat deposition and inflammation in BAT, and stimulated sympathetic nerve activity.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009828 Oleanolic Acid A pentacyclic triterpene that occurs widely in many PLANTS as the free acid or the aglycone for many SAPONINS. It is biosynthesized from lupane. It can rearrange to the isomer, ursolic acid, or be oxidized to taraxasterol and amyrin. Oleanol,Hederins,Oleanane Triterpenes,Triterpenes, Oleanane
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D001933 Brain Stem The part of the brain that connects the CEREBRAL HEMISPHERES with the SPINAL CORD. It consists of the MESENCEPHALON; PONS; and MEDULLA OBLONGATA. Brainstem,Truncus Cerebri,Brain Stems,Brainstems,Cerebri, Truncus,Cerebrus, Truncus,Truncus Cerebrus
D002001 Adipose Tissue, Brown A thermogenic form of adipose tissue composed of BROWN ADIPOCYTES. It is found in newborns of many species including humans, and in hibernating mammals. Brown fat is richly vascularized, innervated, and densely packed with MITOCHONDRIA which can generate heat directly from the stored lipids. Brown Fat,Hibernating Gland,Brown Adipose Tissue,Fat, Brown,Tissue, Brown Adipose
D004734 Energy Metabolism The chemical reactions involved in the production and utilization of various forms of energy in cells. Bioenergetics,Energy Expenditure,Bioenergetic,Energy Expenditures,Energy Metabolisms,Expenditure, Energy,Expenditures, Energy,Metabolism, Energy,Metabolisms, Energy
D000071248 Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha A transcriptional co-activator for NUCLEAR RECEPTORS. It is characterized by an N-terminal LxxLL sequence, a region that interacts with PPAR GAMMA, and a C-terminal RNA RECOGNITION MOTIF. It increases expression of MITOCHONDRIAL UNCOUPLING PROTEIN to regulate genes involved in metabolic reprogramming in response to dietary restriction and the integration of CIRCADIAN RHYTHMS with ENERGY METABOLISM. PGC-1-alpha Protein,PPARGC-1-alpha Protein,PPARGC1a Protein,PGC 1 alpha Protein,PPARGC 1 alpha Protein,Peroxisome Proliferator Activated Receptor Gamma Coactivator 1 alpha

Related Publications

Chi H L Dinh, and Alexander Szabo, and Yinghua Yu, and Danielle Camer, and Qingsheng Zhang, and Hongqin Wang, and Xu-Feng Huang
July 2019, European journal of pharmacology,
Chi H L Dinh, and Alexander Szabo, and Yinghua Yu, and Danielle Camer, and Qingsheng Zhang, and Hongqin Wang, and Xu-Feng Huang
July 2023, The Journal of nutritional biochemistry,
Chi H L Dinh, and Alexander Szabo, and Yinghua Yu, and Danielle Camer, and Qingsheng Zhang, and Hongqin Wang, and Xu-Feng Huang
January 2013, PloS one,
Chi H L Dinh, and Alexander Szabo, and Yinghua Yu, and Danielle Camer, and Qingsheng Zhang, and Hongqin Wang, and Xu-Feng Huang
January 2020, International journal of medical sciences,
Chi H L Dinh, and Alexander Szabo, and Yinghua Yu, and Danielle Camer, and Qingsheng Zhang, and Hongqin Wang, and Xu-Feng Huang
July 2022, Food & function,
Chi H L Dinh, and Alexander Szabo, and Yinghua Yu, and Danielle Camer, and Qingsheng Zhang, and Hongqin Wang, and Xu-Feng Huang
September 2021, The British journal of nutrition,
Chi H L Dinh, and Alexander Szabo, and Yinghua Yu, and Danielle Camer, and Qingsheng Zhang, and Hongqin Wang, and Xu-Feng Huang
February 2022, International journal of obesity (2005),
Chi H L Dinh, and Alexander Szabo, and Yinghua Yu, and Danielle Camer, and Qingsheng Zhang, and Hongqin Wang, and Xu-Feng Huang
January 2016, Journal of nutritional science,
Chi H L Dinh, and Alexander Szabo, and Yinghua Yu, and Danielle Camer, and Qingsheng Zhang, and Hongqin Wang, and Xu-Feng Huang
January 2021, Frontiers in pharmacology,
Chi H L Dinh, and Alexander Szabo, and Yinghua Yu, and Danielle Camer, and Qingsheng Zhang, and Hongqin Wang, and Xu-Feng Huang
July 2011, FEBS letters,
Copied contents to your clipboard!