Adaptive thermogenesis in mice requires adipocyte light-sensing via Opsin 3

Abstract

Almost all life forms can decode light information for adaptive advantage. Examples include the visual system, where photoreceptor signals are interpreted as images, and the circadian system, where light entrains a physiological clock. Here we describe a local, nonvisual light response in mice that employs encephalopsin (OPN3, a 480 nm, blue light responsive opsin) to regulate the function of adipocytes. Germ line null and adipocytespecific conditional null mice show a deficit in thermogenesis that is phenocopied in mice under blue-light deficient conditions. We show that blue light stimulation of adipocytes activates hormone sensitive lipase, the rate limiting enzyme in the lipolysis pathway, and that this is OPN3-dependent. Opn3 adipocyte conditional null mice also use reduced levels of fat mass when fasted and cold exposed further suggesting a lipolysis deficit. These data suggest the hypothesis that in mice, a local, OPN3-dependent light response in adipocytes is a mechanism for regulation of energy homeostasis.