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 
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/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.