title: DJ-1 maintains energy and glucose homeostasis by regulating the function of brown adipose tissue.
abstract: DJ-1 protein is involved in multiple physiological processes, including Parkinson's disease. However, the role of DJ-1 in the metabolism is largely unknown. Here we found that DJ-1 maintained energy balance and glucose homeostasisvia regulating brown adipose tissue (BAT) activity. DJ-1-deficient mice reduced body mass, increased energy expenditure and improved insulin sensitivity. DJ-1 deletion also resisted high-fat-diet (HFD) induced obesity and insulin resistance. Accordingly, DJ-1 transgene triggered autonomous obesity and glucose intolerance. Further BAT transplantation experiments clarified DJ-1 regulates energy and glucose homeostasis by modulating BAT function. Mechanistically, we found that DJ-1 promoted PTEN proteasomal degradation via an E3 ligase, mind bomb-2 (Mib2), which led to Akt activation and inhibited FoxO1-dependent Ucp1 (Uncoupling protein-1) expression in BAT. Consistently, ablation of Akt1 mitigated the obesity and BAT dysfunction induced by DJ-1 transgene. These findings define a new biological role of DJ-1 protein in regulating BAT function, with an implication of the therapeutic target in the treatment of metabolic disorders.
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; College of life science and agronomy, Zhoukou Normal University, Zhoukou, China.
authors.forename: Xiao-Meng
authors.initials: XM
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; Sino-Danish Center Neuroscience Program, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Jian-Guang
authors.initials: JG
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences , Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences , Beijing, China.
authors.forename: Shengyi
authors.initials: S
authors.lastname: Peng
authors.affiliation: Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine , Shanghai, China.
authors.forename: Ji-Qiu
authors.initials: JQ
authors.lastname: Wang
authors.affiliation: Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine , Shanghai, China.
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Ding
authors.affiliation: Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Yanbian University , Yanji, China.
authors.forename: Dong-Hao
authors.initials: DH
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Developmental Biology (Beijing), Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China; Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: John R
authors.initials: JR
authors.lastname: Speakman
authors.affiliation: Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine , Shanghai, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing, China.
authors.forename: Wanzhu
authors.initials: W
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences , Beijing, China.
authors.forename: Zengqiang
authors.initials: Z
authors.lastname: Yuan
keywords: BAT; DJ-1; Ucp1; obesity; ubiquitination