Research ResourceCell Biology

A high-throughput, image-based screen to identify kinases involved in brown adipocyte development

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Science Signaling  14 Feb 2017:
Vol. 10, Issue 466, eaaf5357
DOI: 10.1126/scisignal.aaf5357

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Finding the kinases that power brown fat

Obesity and its associated health risks are a critical and growing problem. Unlike white adipocytes, which store energy, brown adipocytes dissipate energy in the form of heat. Expansion or activation of brown fat has been proposed as a strategy to combat obesity. Using high-throughput analysis that combined RNA interference with pharmacological inhibitors, Perdikari et al. identified kinases that affected brown adipocyte proliferation, differentiation, or formation (when these cells acquire the ability to dissipate energy as heat). Of the 190 brown fat–regulating kinases, they investigated in detail the role of AMPK in promoting the formation of brown adipocytes. Their results highlight kinases that could be therapeutically targeted to enhance the development and function of brown fat.


Brown adipose tissue (BAT) is responsible for thermogenesis that is not associated with shivering through the process of converting chemical energy into heat through uncoupling protein 1 (UCP1) in the mitochondria. Thus, expanding or activating BAT could be a potential tool against obesity. To analyze the effect of kinase signaling on brown adipocyte formation, a process that describes the acquisition of the ability to dissipate energy as heat, we performed lentiviral-mediated short hairpin knockdown or used pharmacological inhibitors in a high-content and high-throughput in vitro image-based screen. We identified 190 kinases that either stimulated or inhibited brown adipocyte proliferation, differentiation, or formation. Among these kinases, we found that 5′ AMP–activated protein kinase (AMPK) promoted the formation of brown adipocytes abundant inUCP1. Together, our results provide insight into the kinases, particularly AMPK, that regulate brown adipocyte formation.

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