Optogenetic activation of UCP1-dependent thermogenesis in brown adipocytes

光遗传学激活棕色脂肪细胞中 UCP1 依赖的产热作用

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作者:Chad C Doucette, Daniel C Nguyen, Davide Barteselli, Sophia Blanchard, Mason Pelletier, Devesh Kesharwani, Ed Jachimowicz, Su Su, Michele Karolak, Aaron C Brown

Abstract

Brown adipocytes are unique in that they expend energy and produce heat to maintain euthermia through expression of uncoupling protein-1 (UCP1). Given their propensity to stimulate weight loss and promote resistance to obesity, they are a compelling interventional target for obesity-related disorders. Here, we tested whether an optogenetic approach could be used to activate UCP1-dependent thermogenesis in brown adipocytes. We generated brown adipocytes expressing a bacterial-derived photoactivatable adenylyl cyclase (bPAC) that, upon blue light stimulation, increases UCP1 expression, fuel uptake and thermogenesis. This unique system allows for precise, chemical free, temporal control of UCP1-dependent thermogenesis, which can aid in our understanding of brown adipocyte biology and development of therapies that target obesity-related disorders.

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