The inhibition of JAK signaling promotes the conversion from white to brown adipocytes


Obesity remains to be topped health issue all over the world, due to the related disorders like diabetes and heart disease. As a therapeutic strategy against obesity, conversion of white adipocytes to brown adipocytes, which have higher metabolic rate than the former, has becoming a promising direction of research. By using a screening platform of small molecules identification, Moisan et al. found two inhibitors of Janus kinase (JAK) signaling were able to convert white adipocytes to brown adipocytes. The article was published online on Nature Cell Biology, recently.


In mammals, white adipose tissue (WAT) in responsibility to store energy. In contrast to WAT, brown adipose tissue (BAT) involved energy release, as well as body temperature maintenance, plasma triglycerides clearance, and insulin resistance improvement. Researchers found two inhibitors of JAK-STAT1/3 pathway, tofacitinib and R406, promoted a white-to-brown metabolic conversion in both human pluripotent stem cell (PSC)-derived adipocytes and human primary adipocytes. In addition, the two inhibitors may function through remodelling lipid droplet morphology. They elevated the expression of uncoupling protein 1 (UCP1), a critical factor in BAT-induced energy release, and increased activities of mitochondrial, via downregulating interferon (IFN) and consequentially activating hedgehog signaling pathway. In conclusion, the two inhibitors targeting JAK-STAT1/3 pathway have the ability to induce brown-like properties to white adipocytes, and they may hold a promising therapeutics effect in amelioration obesity-related disease.


Nat Cell Bio. 2014 Dec 8;10.1038/ncb3075.

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