Lin Yi-Wen, Cheng Szu-Wei, Liu Wen-Chun, Zailani Halliru, Wu Suet-Kei, Hung Mien-Chie, Su Kuan-Pin
Graduate Institute of Acupuncture Science, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan; Chinese Medicine Research Center, China Medical University, Taichung 40402, Taiwan.
Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung, Taiwan.
Brain Behav Immun. 2025 Jan;123:771-783. doi: 10.1016/j.bbi.2024.10.028. Epub 2024 Oct 23.
The comorbidity of obesity and depression has major public health impacts, highlighting the need to understand their shared mechanisms. This study explored the connection between obesity and depression through the transient receptor potential V1 (TRPV1) signaling pathway, using obese/depressed murine models and clinical data. Mice fed a high-fat diet showed altered TRPV1 pathway expression in brain regions of the mice: downregulated in the medial prefrontal cortex (mPFC) and hippocampus, and upregulated in the hypothalamus and amygdala, influencing depression-like behaviors and inflammation. Treatments like eicosapentaenoic acid (EPA) and acupoint catgut embedding (ACE) reversed these effects, similar to observations in Trpv1 mice. Furthermore, chemogenetic activation in the ventral mPFC also alleviated depression via TRPV1. In our clinical validation, single nucleotide polymorphisms (SNPs) in TRPV1-related genes (PIK3C2A and PRKCA) were linked to interferon-induced depression. These findings underscore the potential of targeting TRPV1 as a therapeutic approach for obesity-related depression.
肥胖与抑郁症的共病对公共卫生有重大影响，凸显了了解其共同机制的必要性。本研究利用肥胖/抑郁小鼠模型和临床数据，通过瞬时受体电位香草酸亚型1（TRPV1）信号通路探讨肥胖与抑郁症之间的联系。喂食高脂饮食的小鼠在大脑区域的TRPV1通路表达发生改变：内侧前额叶皮质（mPFC）和海马体中表达下调，而下丘脑和杏仁核中表达上调，影响抑郁样行为和炎症反应。二十碳五烯酸（EPA）和穴位埋线（ACE）等治疗可逆转这些效应，类似于在Trpv1基因敲除小鼠中的观察结果。此外，腹侧mPFC中的化学遗传学激活也通过TRPV1减轻了抑郁症状。在我们的临床验证中，TRPV1相关基因（PIK3C2A和PRKCA）中的单核苷酸多态性（SNP）与干扰素诱导的抑郁症有关。这些发现强调了将TRPV1作为肥胖相关抑郁症治疗靶点的潜力。
