title: JAK2 promotes brown adipose tissue function and is required for diet- and cold-induced thermogenesis in mice.
abstract: OBJECTIVE
  Non-shivering thermogenesis in adipose tissue can be activated by excessive energy intake or following cold exposure. The molecular mechanisms regulating this activation have not been fully elucidated. The Janus kinase (JAK) - signal transducer and activator of transcription (STAT) pathway mediates the signal transduction of numerous hormones and growth factors that regulate adipose tissue development and function, and may play a role in adaptive thermogenesis.
  
  
  METHODS
  We analysed mRNA and protein levels of uncoupling protein 1 (UCP1) and JAK2 in different adipose depots in response to metabolic and thermal stress. The in vivo role of JAK2 in adaptive thermogenesis was examined using mice with adipocyte-specific Jak2 deficiency (A-Jak2 KO).
  
  
  RESULTS
  We show in murine brown adipose tissue (BAT) that JAK2 is upregulated together with UCP1 in response to high-fat diet (HFD) feeding and cold exposure. In contrast to white adipose tissue, where JAK2 was dispensable for UCP1 induction, we identified an essential role for BAT JAK2 in diet- and cold-induced thermogenesis via mediating the thermogenic response to β-adrenergic stimulation. Accordingly, A-Jak2 KO mice were unable to upregulate BAT UCP1 following a HFD or after cold exposure. Therefore, A-Jak2 KO mice were cold intolerant and susceptible to HFD-induced obesity and diabetes.
  
  
  CONCLUSIONS
  Taken together, our results suggest that JAK2 plays a critical role in BAT function and adaptive thermogenesis. Targeting the JAK-STAT pathway may be a novel therapeutic approach for the treatment of obesity and related metabolic disorders.
authors.affiliation: Toronto General Research Institute, 101 College Street, MaRS Centre/TMDT, Toronto, ON, Canada, M5G 1L7.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Sally Yu
authors.initials: SY
authors.lastname: Shi
authors.affiliation: Toronto General Research Institute, 101 College Street, MaRS Centre/TMDT, Toronto, ON, Canada, M5G 1L7.|Department of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Toronto General Research Institute, 101 College Street, MaRS Centre/TMDT, Toronto, ON, Canada, M5G 1L7.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Cynthia T
authors.initials: CT
authors.lastname: Luk
authors.affiliation: Toronto General Research Institute, 101 College Street, MaRS Centre/TMDT, Toronto, ON, Canada, M5G 1L7.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Tharini
authors.initials: T
authors.lastname: Sivasubramaniyam
authors.affiliation: Toronto General Research Institute, 101 College Street, MaRS Centre/TMDT, Toronto, ON, Canada, M5G 1L7.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Jara J
authors.initials: JJ
authors.lastname: Brunt
authors.affiliation: Toronto General Research Institute, 101 College Street, MaRS Centre/TMDT, Toronto, ON, Canada, M5G 1L7.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Schroer
authors.affiliation: Toronto General Research Institute, 101 College Street, MaRS Centre/TMDT, Toronto, ON, Canada, M5G 1L7.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Harsh R
authors.initials: HR
authors.lastname: Desai
authors.affiliation: Toronto General Research Institute, 101 College Street, MaRS Centre/TMDT, Toronto, ON, Canada, M5G 1L7.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Majerski
authors.affiliation: Toronto General Research Institute, 101 College Street, MaRS Centre/TMDT, Toronto, ON, Canada, M5G 1L7. mwoo@uhnresearch.ca.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada. mwoo@uhnresearch.ca.|Division of Endocrinology, Department of Medicine, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON, Canada. mwoo@uhnresearch.ca.
authors.forename: Minna
authors.initials: M
authors.lastname: Woo
mesh_terms: D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis; D002001:Adipose Tissue, Brown / Q000502:physiology*; D052436:Adipose Tissue, White / Q000502:physiology; D050154:Adiposity; D000818:Animals; D059305:Diet, High-Fat; D005260:Female; D007328:Insulin / Q000502:physiology; D007473:Ion Channels / Q000502:physiology; D053613:Janus Kinase 1 / Q000502:physiology; D053614:Janus Kinase 2 / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000502:physiology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000502:physiology; D015398:Signal Transduction; D022722:Thermogenesis; D000071256:Uncoupling Protein 1; D015854:Up-Regulation
chemical_list: D007328:Insulin; D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C507926:Jak2 protein, mouse; D053613:Janus Kinase 1; D053614:Janus Kinase 2
keywords: Adaptive thermogenesis; Brown adipose tissue; Diabetes; Glucose homeostasis; Janus kinase 2 (JAK2); Obesity; Uncoupling protein 1 (UCP1)