2. Academic Validation
  3. LXRs agonists alleviate fat transplantation-induced cognitive dysfunction by inhibiting STING-dependent type I interferon response

LXRs agonists alleviate fat transplantation-induced cognitive dysfunction by inhibiting STING-dependent type I interferon response

  • Int Immunopharmacol. 2026 Mar 1:172:116229. doi: 10.1016/j.intimp.2026.116229.
Juan Li 1,  Yanqiong Wu 2,  Fan Jiang 1,  Yijing Li 1,  Kun Chen 3,  Zhixiao Li 1,  Changbin Ke 4,  Hongbing Xiang 5
Affiliations

Affiliations

  • 1 Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 2 Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Institute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
  • 3 Department of Anesthesiology, Wenchang People's Hospital, Wenchang, China.
  • 4 Institute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China. Electronic address: [email protected].
  • 5 Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan 430030, China.. Electronic address: [email protected].
PMID: 41558290 DOI: 10.1016/j.intimp.2026.116229
Abstract

Cognitive decline is a comorbidity of neuropathic pain, and is associated with adipose tissue metabolism. We identified that adipose tissue was related to cognitive dysfunction caused by neuropathic pain by constructing adipose tissue transplantation model. We also observed increased expression of dsDNA in mice with cognitive dysfunction, which activated the cGAS-STING pathway, concurrently triggering a type I interferon response and microglial activation. LXRβ also plays a significant role in cognitive dysfunction. LXRβ agonist can ameliorate cognitive dysfunction caused by adipose transplantation by inhibiting the cGAS-STING DNA-sensing pathway. Our findings suggest that LXRβ and the cGAS-STING pathway play key roles in the communication between adipose tissue and the central nervous system, providing novel targets and directions for the treatment of cognitive dysfunction.

Keywords

Adipose tissue transplantation; Cognitive dysfunction; IFN-I; LXRβ; cGAS-STING.

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