title: Adipocyte-specific deficiency of Janus kinase (JAK) 2 in mice impairs lipolysis and increases body weight, and leads to insulin resistance with ageing.
abstract: OBJECTIVE
  The growing obesity epidemic necessitates a better understanding of adipocyte biology and its role in metabolism. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway mediates signalling by numerous cytokines and hormones that regulate adipocyte function, illustrating the physiological importance of adipose JAK-STAT. The aim of this study was to investigate potential roles of adipocyte JAK2, an essential player in the JAK-STAT pathway, in adipocyte biology and metabolism.
  
  
  METHODS
  We generated adipocyte-specific Jak2 knockout (A-Jak2 KO) mice using the Cre-loxP system with Cre expression driven by the Ap2 (also known as Fabp4) promoter.
  
  
  RESULTS
  Starting at 2-3 months of age, male and female A-Jak2 KO mice gradually gained more body weight than control littermates primarily due to increased adiposity. This was associated with reduced energy expenditure in A-Jak2 KO mice. In perigonadal adipose tissue, the expression of numerous genes involved in lipid metabolism was differentially regulated. In addition, adipose tissue from A-Jak2 KO mice displayed impaired lipolysis in response to isoprenaline, growth hormone and leptin stimulation, suggesting that adipose JAK2 directly modulates the lipolytic program. Impaired lipid homeostasis was also associated with disrupted adipokine secretion. Accordingly, while glucose metabolism was normal at 2 months of age, by 5-6 months of age, A-Jak2 KO mice had whole-body insulin resistance.
  
  
  CONCLUSIONS
  Our results suggest that adipocyte JAK2 plays a critical role in the regulation of adipocyte biology and whole-body metabolism. Targeting of the JAK-STAT pathway could be a novel therapeutic option for the treatment of obesity and type 2 diabetes.
authors: Toronto General Research Institute, 101 College Street, MaRS Centre/TMDT, Room 10-363, Toronto, ON, Canada, M5G 1L7.
authors: Sally Yu
authors: SY
authors: Shi
authors: Cynthia T
authors: CT
authors: Luk
authors: Jara J
authors: JJ
authors: Brunt
authors: Tharini
authors: T
authors: Sivasubramaniyam
authors: Shun-Yan
authors: SY
authors: Lu
authors: Stephanie A
authors: SA
authors: Schroer
authors: Minna
authors: M
authors: Woo
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D054392:Adipokines; D050154:Adiposity; D000375:Aging; D000818:Animals; D001823:Body Composition; D001835:Body Weight; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D053614:Janus Kinase 2 / Q000378:metabolism*; D008066:Lipolysis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity; D011401:Promoter Regions, Genetic
chemical_list: D054392:Adipokines; D016207:Cytokines; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2