2. Academic Validation
  3. Microglial Feimin Alleviates Cognitive Impairment in High-Fat Diet-Fed Mice

Microglial Feimin Alleviates Cognitive Impairment in High-Fat Diet-Fed Mice

  • Adv Sci (Weinh). 2025 Oct 20:e12023. doi: 10.1002/advs.202512023.
Ran Gao 1 2,  Zhonghua Xiong 3,  Wenting Su 1 2,  Jiahui Deng 4 2 5,  Bin Zhai 6,  Gaizhi Zhu 1 2,  Min Zhang 1 2,  Qi Zeng 1 2,  Jinming Qiu 1 2,  Ziqing Bian 1 2,  He Xiao 7,  Guoming Luan 4 2 5,  Renxi Wang 1 2
Affiliations

Affiliations

  • 1 Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, 100069, China.
  • 2 Laboratory for Clinical Medicine, Capital Medical University, Beijing, 100069, China.
  • 3 Headache Center, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
  • 4 Department of Neurosurgery, SanBo Brain Hospital, Capital Medical University, Beijing, 100093, China.
  • 5 Beijing Key Laboratory of Epilepsy Research, Department of Brain Institute, Center of Epilepsy, Beijing Institute for Brain Disorders, Sanbo Brain Hospital, Capital Medical University, Beijing, 100069, China.
  • 6 Department of Hematology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, China.
  • 7 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
PMID: 41114468 DOI: 10.1002/advs.202512023
Abstract

Lipid droplet accumulation in microglia, microglia-mediated neuroinflammation, and subsequent neuronal damage are hallmark features of high-fat diet (HFD)-induced cognitive impairment. In this analysis, this is proposed that a new molecule feimin (B230219D22Rik in mice) is a key negative regulator of LD accumulation and the inflammatory response in HFD-induced cognitive impairment. To test this hypothesis, BV2 microglia is exposed to palmitic acid (PA) in vitro, mimicking the effects of an HFD. This is found that feimin expression is significantly increased following high-lipid stimulation. Feimin-specific knockdown in BV2 cells led to enhanced LD accumulation, exacerbated inflammatory responses and neuronal Apoptosis, whereas feimin overexpression has the opposite effect. Mechanistically, immunoprecipitation (IP) assays revealed that an interaction between feimin and Akt suppressed the AKT-mTOR signaling pathway. To further investigate the role of feimin in vivo, microglial feimin-conditional knockout mice (feiminMic-/-) is developed. In the HFD model, feiminMic-/- mice exhibited increased LD accumulation in hippocampal microglia, enhanced inflammation, and neuronal Apoptosis, resulting in significant cognitive decline. In conclusion, this findings identified feimin as a key negative regulator of HFD-induced LD accumulation and the microglia-mediated inflammation response, suggesting that it is an attractive therapeutic target for cognitive decline associated with HFDs.

Keywords

B230219D22Rik; BV2; Feimin; High‐fat diets; Hippocampus; Lipid droplets; Neuroinflammation; Palmitic acid.

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