title: Transcription regulator TRIP-Br2 mediates ER stress-induced brown adipocytes dysfunction.
abstract: In contrast to white adipose tissue, brown adipose tissue (BAT) is known to play critical roles for both basal and inducible energy expenditure. Obesity is associated with reduction of BAT function; however, it is not well understood how obesity promotes BAT dysfunction, especially at the molecular level. Here we show that the transcription regulator TRIP-Br2 mediates ER stress-induced inhibition of lipolysis and thermogenesis in BAT. Using in vitro, ex vivo, and in vivo approaches, we demonstrate that obesity-induced inflammation upregulates brown adipocytes TRIP-Br2 expression via the ER stress pathway and amelioration of ER stress in mice completely abolishes high fat diet-induced upregulation of TRIP-Br2 in BAT. We find that increased TRIP-Br2 significantly inhibits brown adipocytes thermogenesis. Finally, we show that ablation of TRIP-Br2 ameliorates ER stress-induced inhibition on lipolysis, fatty acid oxidation, oxidative metabolism, and thermogenesis in brown adipocytes. Taken together, our current study demonstrates a role for TRIP-Br2 in ER stress-induced BAT dysfunction, and inhibiting TRIP-Br2 could be a potential approach for counteracting obesity-induced BAT dysfunction.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and Beijing Key Laboratory of Drug Target and Screening Research, Beijing, 100050, China.|Department of Physiology &Biophysics, College of Medicine, University of Illinois at Chicago, 835 S Wolcott Ave, M/C901, Chicago, IL, 60612, United States.
authors.forename: Guifen
authors.initials: G
authors.lastname: Qiang
authors.affiliation: Department of Physiology &Biophysics, College of Medicine, University of Illinois at Chicago, 835 S Wolcott Ave, M/C901, Chicago, IL, 60612, United States.
authors.forename: Hyerim
authors.initials: H
authors.lastname: Whang Kong
authors.affiliation: Department of Physiology &Biophysics, College of Medicine, University of Illinois at Chicago, 835 S Wolcott Ave, M/C901, Chicago, IL, 60612, United States.
authors.forename: Victoria
authors.initials: V
authors.lastname: Gil
authors.affiliation: Department of Physiology &Biophysics, College of Medicine, University of Illinois at Chicago, 835 S Wolcott Ave, M/C901, Chicago, IL, 60612, United States.
authors.forename: Chong Wee
authors.initials: CW
authors.lastname: Liew
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat; D059865:Endoplasmic Reticulum Stress; D008066:Lipolysis; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*; D022722:Thermogenesis; D014157:Transcription Factors / Q000378:metabolism*; D000092468:Bromodomain Containing Proteins
chemical_list: D014157:Transcription Factors; C486065:Sertad2 protein, mouse; D000092468:Bromodomain Containing Proteins