Optogenetic activation of UCP1-dependent thermogenesis in brown adipocytes

利用光遗传学方法激活棕色脂肪细胞中UCP1依赖性产热

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作者:Chad C Doucette,Daniel C Nguyen,Davide Barteselli,Sophia Blanchard,Masen 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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