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

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. [Display omitted] •Adipocytes express encephalopsin (OPN3), a 480 nm blue-light-sensitive opsin•Mice lacking OPN3 or blue light have diminished thermogenesis during cold exposure•Loss of OPN3 reduces oxygen consumption and energy expenditure•White adipocyte OPN3 promotes lipolysis during cold exposure White adipocytes activate the lipolysis pathway to produce the free fatty acids that are used as heating fuel by brown adipose tissue. Nayak et al. show that Opsin 3 is required for blue-light-enhanced activation of the lipolysis pathway. This explains the low body temperature of Opn3 mutant mice.