PLX080633

GSE140764: Light effect via Opn3 on the activity of brown adipocytes

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Opsin3 (Opn3) is a transmembrane heptahelical G-protein-coupled receptor (GPCR) with the potential to produce a non-visual photoreceptive effect. Interestingly, anatomical profiling of GPCRs reveals that Opn3 mRNA is highly expressed in adipose tissue. The photosensitive functions of Opn3 in mammals are poorly understood, and whether Opn3 has a function in fat is entirely unknown. In this study, we found that Opn3-knockout (Opn3-KO) mice were prone to diet-induced obesity and insulin-resistance. At the cellular level, Opn3-KO brown adipocytes cultured in darkness had decreased glucose uptake and lower nutrient-induced mitochondrial respiration than wild-type (WT) cells. Light exposure promoted mitochondrial activity and glucose uptake in WT adipocytes but not in Opn3-KO cells. Using RNA sequencing, we identified several novel light-sensitive and Opn3-dependent molecular signatures in brown adipocytes. Importantly, direct exposure of BAT to light in living mice significantly enhanced thermogenic capacity of BAT, and this effect was diminished in Opn3-KO animals. These results uncover a previously unrecognized cell-autonomous, light-sensing mechanism in brown adipocytes via Opn3-GPCR signaling that can regulate fuel metabolism and mitochondrial respiration in vitro and thermogenesis in vivo. Our work also provides a molecular basis for developing light-based treatments for obesity and its related metabolic disorders. SOURCE: Hui Pan (Hui.Pan@joslin.harvard.edu) - Joslin Diabetes Center