Tsuji Tadataka, Tolstikov Vladimir, Zhang Yang, Huang Tian Lian, Camara Henrique, Halpin Meghan, Narain Niven R, Yau King-Wai, Lynes Matthew D, Kiebish Michael A, Tseng Yu-Hua
Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
BPGbio, Framingham, MA, USA.
Nat Commun. 2024 Aug 8;15(1):6768. doi: 10.1038/s41467-024-50866-0.
Light is fundamental for biological life, with most mammals possessing light-sensing photoreceptors in various organs. Opsin3 is highly expressed in adipose tissue which has extensive communication with other organs, particularly with the brain through the sympathetic nervous system (SNS). Our study reveals a new light-triggered crosstalk between adipose tissue and the hypothalamus. Direct blue-light exposure to subcutaneous white fat improves high-fat diet-induced metabolic abnormalities in an Opsin3-dependent manner. Metabolomic analysis shows that blue light increases circulating levels of histidine, which activates histaminergic neurons in the hypothalamus and stimulates brown adipose tissue (BAT) via SNS. Blocking central actions of histidine and denervating peripheral BAT blunts the effects of blue light. Human white adipocytes respond to direct blue light stimulation in a cell-autonomous manner, highlighting the translational relevance of this pathway. Together, these data demonstrate a light-responsive metabolic circuit involving adipose-hypothalamus communication, offering a potential strategy to alleviate obesity-induced metabolic abnormalities.
光对于生物生命至关重要，大多数哺乳动物的各个器官都拥有光感应光感受器。视蛋白3在脂肪组织中高度表达，脂肪组织与其他器官，特别是通过交感神经系统（SNS）与大脑有着广泛的联系。我们的研究揭示了脂肪组织与下丘脑之间一种新的光触发串扰。直接蓝光照射皮下白色脂肪以视蛋白3依赖的方式改善高脂饮食诱导的代谢异常。代谢组学分析表明，蓝光会增加循环中的组氨酸水平，组氨酸会激活下丘脑的组胺能神经元，并通过交感神经系统刺激棕色脂肪组织（BAT）。阻断组氨酸的中枢作用并去除外周棕色脂肪组织的神经支配会减弱蓝光的作用。人类白色脂肪细胞以细胞自主的方式对直接蓝光刺激做出反应，突出了该途径的转化相关性。总之，这些数据证明了一个涉及脂肪-下丘脑通讯的光响应代谢回路，为缓解肥胖诱导的代谢异常提供了一种潜在策略。
