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JAK2 promotes brown adipose tissue function and is required for diet- and cold-induced thermogenesis in mice.

Authors: Shi, SY  Zhang, W  Luk, CT  Sivasubramaniyam, T  Brunt, JJ  Schroer, SA  Desai, HR  Majerski, A  Woo, M 
Citation: Shi SY, etal., Diabetologia. 2016 Jan;59(1):187-96. doi: 10.1007/s00125-015-3786-2. Epub 2015 Oct 29.
Pubmed: (View Article at PubMed) PMID:26515423
DOI: Full-text: DOI:10.1007/s00125-015-3786-2

AIMS/HYPOTHESIS: 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 beta-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/INTERPRETATION: 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.


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RGD Object Information
RGD ID: 11354746
Created: 2016-07-27
Species: All species
Last Modified: 2016-07-27
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.