Adipocytes are now recognized as active endocrine cells with indispensable physiological functions. Alterations in adipocyte development and/or function have been implicated in the pathophysiology of type 2 diabetes. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway mediates signalling by numerous cytokines and hormones that regulate adipocyte function. Several cytokines secreted by adipocytes also utilize this pathway, illustrating the physiological importance of JAK-STATs in adipocyte biology. We sought to investigate potential metabolic roles of adipose JAK2 using adipocyte-specific JAK2 knockout (F-JAK2 KO) mice generated using the Cre-loxP system with Cre expression driven by the aP2 promoter. Starting at 2 to 3 months of age, F-JAK2 KO mice on a chow diet gradually gained more body weight compared to control littermates. This was primarily due to increased adiposity, accompanied by increased leptin and decreased adiponectin levels in the circulation. To determine the underlying basis for the increased adiposity, energy balance was assessed using indirect calorimetry. Daily food intake was not changed, whereas energy expenditure and physical activity were significantly reduced in F-JAK2 KO mice. In the perigonadal adipose tissue, an increase in expression of hormone sensitive lipase (Hsl) and a reduction in adipose triglyceride lipase (Atgl) were observed, suggesting dysregulated lipolysis. Accordingly, while glucose metabolism was normal at 2 months of age, by 5 to 6 months, F-JAK2 KO mice became more glucose intolerant and insulin resistant. Thus, adipocyte JAK2 plays a critical role in metabolism and may constitute a novel therapeutic target for the treatment of obesity and type 2 diabetes.
© 2013 Published by Elsevier Inc.