Adaptive Thermogenesis in Mice Is Enhanced by Opsin 3-Dependent Adipocyte Light Sensing

视蛋白3依赖性脂肪细胞光感应增强小鼠的适应性产热

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作者:Gowri Nayak ,Kevin X Zhang ,Shruti Vemaraju ,Yoshinobu Odaka ,Ethan D Buhr ,Amanda Holt-Jones ,Stace Kernodle ,April N Smith ,Brian A Upton ,Shane D'Souza ,Jesse J Zhan ,Nicolás Diaz ,Minh-Thanh Nguyen ,Rajib Mukherjee ,Shannon A Gordon ,Gang Wu ,Robert Schmidt ,Xue Mei ,Nathan T Petts ,Matthew Batie ,Sujata Rao ,John B Hogenesch ,Takahisa Nakamura ,Alison Sweeney ,Randy J Seeley ,Russell N Van Gelder ,Joan Sanchez-Gurmaches ,Richard A Lang

Abstract

Almost all life forms can detect and decode light information for adaptive advantage. Examples include the visual system, in which photoreceptor signals are processed into virtual images, and the circadian system, in which light entrains a physiological clock. Here we describe a light response pathway in mice that employs encephalopsin (OPN3, a 480 nm, blue-light-responsive opsin) to regulate the function of adipocytes. Germline null and adipocyte-specific conditional null mice show a light- and Opn3-dependent deficit in thermogenesis and become hypothermic upon cold exposure. We show that stimulating mouse adipocytes with blue light enhances the lipolysis response and, in particular, phosphorylation of hormone-sensitive lipase. This response is Opn3 dependent. These data establish a key mechanism in which light-dependent, local regulation of the lipolysis response in white adipocytes regulates energy metabolism.

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