表達Opsin 5的下丘腦神經元通過感知紫光抑制產熱
作者：
小柯機器人發布時間：2020/9/3 16:21:24
美國辛辛那提兒童醫院醫學中心Richard A. Lang及其團隊的最新研究表明，表達Opsin 5（也稱為絲氨酸蛋白酶或OPN5）的下丘腦神經元感知紫光並抑制棕色脂肪組織（BAT）的產熱功能。相關論文於2020年9月2日在線發表於《自然》。
研究人員揭示了一種光感通路，其中表達Opn5的下丘腦前視區（POA）神經元調節棕色脂肪組織（BAT）的產熱功能。Opn5在穀氨酸能熱感POA神經元中表達，這些神經元接收了來自幾個體溫調節中心的突觸輸入。進一步表明，Opn5 POA神經元投射到BAT，並在化學刺激下降低其活性。Opn5缺失小鼠在冷刺激時會發生BAT過度激活、體溫升高和過度產熱。
此外，在野生型而非Opn5缺失的小鼠中冷刺激外加紫色光刺激可強烈抑制BAT產熱功能。通過直接測量離體細胞內cAMP，研究人員發現Opn5 POA神經元在受到紫光刺激時會增加cAMP。因此，該研究揭示了大腦內紫色光的感光體，該感光體通常會抑制BAT的產熱功能。
據了解，在動物體中G蛋白偶聯受體視蛋白家族作為光感受器。Opsin 5是高度保守的視蛋白，對可見的紫色光敏感。OPN5是小鼠視網膜和皮膚中已知的感光體，但其也在POA中表達。
附：英文原文
Title: Violet-light suppression of thermogenesis by opsin 5 hypothalamic neurons
Author: Kevin X. Zhang, Shane DSouza, Brian A. Upton, Stace Kernodle, Shruti Vemaraju, Gowri Nayak, Kevin D. Gaitonde, Amanda L. Holt, Courtney D. Linne, April N. Smith, Nathan T. Petts, Matthew Batie, Rajib Mukherjee, Durgesh Tiwari, Ethan D. Buhr, Russell N. Van Gelder, Christina Gross, Alison Sweeney, Joan Sanchez-Gurmaches, Randy J. Seeley, Richard A. Lang
Issue&Volume: 2020-09-02
Abstract: 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 light1,2. In mice, OPN5 is a known photoreceptor in the retina3 and skin4 but is also expressed in the hypothalamic preoptic area (POA)5. Here we describe a light-sensing pathway in which POA neurons that express Opn5 regulate thermogenesis in brown adipose tissue (BAT). We show that Opn5 is expressed in glutamatergic warm-sensing POA neurons that receive synaptic input from several thermoregulatory nuclei. We further show that Opn5 POA 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 in Opn5-null mice. Direct measurements of intracellular cAMP ex vivo show that Opn5 POA neurons increase cAMP when stimulated with violet light. This analysis thus identifies a violet light-sensitive deep brain photoreceptor that normally suppresses BAT thermogenesis. 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.
DOI: 10.1038/s41586-020-2683-0
Source: https://www.nature.com/articles/s41586-020-2683-0