Violet-light suppression of thermogenesis by opsin 5 hypothalamic neurons

Mice possess neurons in the preoptic area of the hypothalamus that are sensitive to violet light; these deep brain neurons sense light via OPN5 and regulate adaptive thermogenesis in brown fat. The opsin family of G-protein-coupled receptors are used as light detectors in animals. Opsin 5 (also known as neuropsin or OPN5) is a highly conserved opsin that is sensitive to visible violet light(1,2). In mice, OPN5 is a known photoreceptor in the retina(3)and skin(4)but is also expressed in the hypothalamic preoptic area (POA)(5). Here we describe a light-sensing pathway in which POA neurons that expressOpn5regulate thermogenesis in brown adipose tissue (BAT). We show thatOpn5is expressed in glutamatergic warm-sensing POA neurons that receive synaptic input from several thermoregulatory nuclei. We further show thatOpn5POA neurons project to BAT and decrease its activity under chemogenetic stimulation.Opn5-null mice show overactive BAT, increased body temperature, and exaggerated thermogenesis when cold-challenged. Moreover, violet photostimulation during cold exposure acutely suppresses BAT temperature in wild-type mice but not inOpn5-null mice. Direct measurements of intracellular cAMP ex vivo show thatOpn5POA neurons increase cAMP when stimulated with violet light. This analysis thus identifies a violet light-sensitive deep brain photoreceptor that normally suppresses BAT thermogenesis.