小柯机器人

美国辛辛那提儿童医院医学中心Richard A. Lang及其团队的最新研究表明，表达Opsin 5（也称为丝氨酸蛋白酶或OPN5）的下丘脑神经元感知紫光并抑制棕色脂肪组织（BAT）的产热功能。相关论文于2020年9月2日在线发表于《自然》。

研究人员揭示了一种光感通路，其中表达Opn5的下丘脑前视区（POA）神经元调节棕色脂肪组织（BAT）的产热功能。Opn5在谷氨酸能热感POA神经元中表达，这些神经元接收了来自几个体温调节中心的突触输入。进一步表明，Opn5 POA神经元投射到BAT，并在化学刺激下降低其活性。Opn5缺失小鼠在冷刺激时会发生BAT过度激活、体温升高和过度产热。

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强烈抑制BAT产热功能。通过直接测量离体细胞内cAMP，研究人员发现Opn5 POA神经元在受到紫光刺激时会增加cAMP。因此，该研究揭示了大脑内紫色光的感光体，该感光体通常会抑制BAT的产热功能。

据了解，在动物体中G蛋白偶联受体视蛋白家族作为光感受器。Opsin 5是高度保守的视蛋白，对可见的紫色光敏感。OPN5是小鼠视网膜和皮肤中已知的感光体，但其也在POA中表达。

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

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