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journal article·2026-03Open access

Dysfunctional TRIM31 of POMC Neurons Provokes Hypothalamic Injury and Peripheral Metabolic Disorder under Long‐Term Fine Particulate Matter Exposure

Chenxu Ge, Jiamao Lin, Changsheng Yang, Chuanwang Miao, Fengxiang Li, Shuqiang Zhao, Lei Zou, Xuedong Teng, Lina Liu, Tingguang Li, Yan Sun, Qiang Li, Deshuai Lou, Linfeng Hu, Xi Liu, Gang Kuang, Jing Luo, Minxuan Xu, Minghui Chang, Jun Tan, Yanrong Ren, Bochu Wang

Advanced Science· Volume 13· Issue 14
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Source abstract

Abstract

ABSTRACT Particulate matter ≤2.5 µm (PM 2.5 ) elevates risks of neurological and chronic metabolic diseases, but the underlying mechanisms linking PM 2.5 ‐induced central nervous system (CNS) injury to metabolic dysfunction remain unclear. Hypothalamic pro‐opiomelanocortin‐expressing (POMC+) neurons regulate systemic metabolic homeostasis, and tripartite motif‐containing protein 31 (TRIM31) modulates inflammation and metabolism. Here, we investigated whether TRIM31 in POMC+ neurons mediates PM 2.5 ‐induced hypothalamic injury and peripheral metabolic disorders in mice subjected to 24‐week PM 2.5 exposure. TRIM31 knockout in POMC + neurons ( POMC Cre/+; TRIM31 flox/flox ) exacerbated PM 2.5 ‐;induced increases in mean blood pressure and fat weight, liver weight reduction, adipocyte hypertrophy, hepatic lipid deposition, energy expenditure abnormalities and insulin resistance. It also aggravated hypothalamic damage (downregulated NeuN, POMC and MC4R) and amplified neuroinflammation and oxidative stress. Conversely, AAV‐mediated TRIM31 overexpression in POMC + neurons alleviated these pathological phenotypes. In vitro, TRIM31 deletion promoted reactive oxygen species (ROS) and inflammation in PM 2.5 ‐challenged hypothalamic neurons and microglia, while TRIM31 overexpression exerted opposite effects; microglial TRIM31 depletion exacerbated neuronal death via conditioned medium. Mechanistically, TRIM31 directly interacted with Nrf2, enhancing its K63‐linked polyubiquitination and reducing K48‐linked polyubiquitination to activate Nrf2 signaling, which was required for TRIM31‐mediated attenuation of neuronal death and inflammation under PM2.5 stress. Collectively, our findings identify the TRIM31/Nrf2 axis as a key molecular switch governing POMC + neuronal loss, hypothalamic injury and consequent peripheral metabolic disorders triggered by long‐term PM 2.5 exposure.
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Research context

Materials processing

OpenAlex topics: interferon and immune responses · Neuroinflammation and Neurodegeneration Mechanisms · Neurogenesis and neuroplasticity mechanisms

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Affiliations

Key Laboratory of Biorheological Science and Technology (Chongqing University) Ministry of Education Chongqing University Chongqing P. R. China

Chongqing Key Laboratory of Functional Substances from Distinctive Medicinal Plants in the Three Gorges Reservoir Area School of Biological and Chemical Engineering Chongqing University of Education Chongqing P. R. China

Research Center of Brain Intellectual Promotion and Development for Children Aged 0‐6 Years Chongqing University of Education Chongqing P. R. China

Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin's Clinical Research Center for Cancer Tianjin China

Department of Orthopedic Oncology Surgery Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences Jinan P. R. China

Department of Radiation Oncology Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences Jinan P. R. China

Department of Gastrointestinal Surgery Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences Jinan P. R. China

Ultrasound Department Yantai Qishan Hospital Yantai P. R. China

Department of General Surgery The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine Jinan P. R. China

Traditional Chinese Medicine Discipline The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine Jinan P. R. China

Tumor Research and Therapy Center Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan P. R. China

Funding

National Natural Science Foundation of China · Chongqing Research Program of Basic Research and Frontier Technology

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