Muscle-derived factor alleviated cognitive impairment caused by intestinal ischemia-reperfusion
Intestinal ischemia/reperfusion (II/R) is a common and grave clinical event, with high morbidity and mortality which can cause cerebral dysfunctions. There are no ideal prevention and treatment measures yet. The present study aimed to determine whether muscle-derived factors can alleviate gut-associ...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-07-01
|
| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231725001958 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850131620577673216 |
|---|---|
| author | Yafang Tan Guo Mu Feixiang Wang Xin Fan Chengjie Yang Zuan Shi Yiping Bai Bingqing Xie Xuan Yu Jianguo Feng Jing Jia Xiaobin Wang Ye Chen Jun Zhou |
| author_facet | Yafang Tan Guo Mu Feixiang Wang Xin Fan Chengjie Yang Zuan Shi Yiping Bai Bingqing Xie Xuan Yu Jianguo Feng Jing Jia Xiaobin Wang Ye Chen Jun Zhou |
| author_sort | Yafang Tan |
| collection | DOAJ |
| description | Intestinal ischemia/reperfusion (II/R) is a common and grave clinical event, with high morbidity and mortality which can cause cerebral dysfunctions. There are no ideal prevention and treatment measures yet. The present study aimed to determine whether muscle-derived factors can alleviate gut-associated cerebral dysfunctions (GACD) following II/R. We measured the tibialis anterior muscle thickness and irisin levels in patients with and without cognitive dysfunction following cardiopulmonary bypass surgery, calculating the correlation between irisin and cognitive impairment. We found that this protective effect is related to muscle-derived irisin. To elucidate the role of irisin in improving GACD, we knocked out FNDC5 to deplete endogenous irisin and supplemented exogenous irisin. Mechanistic insights into irisin's effects on GACD were investigated using in vivo and in vitro models, incorporating techniques such as transmission electron microscopy, protein docking analysis, gene overexpression, and western blotting. FNDC5/irisin deficiency aggravated cognitive impairments, the pro-inflammation microglia activation, oxidative injury, inflammatory response, neuronal apoptosis and ferroptosis, while recombinant FNDC5/irisin reversed the above changes leading to neurostructural and cognition recovery. Mechanistically, thioredoxin-interacting protein (TXNIP) was activated in the II/R-related neuropathology and was deteriorated in FNDC5/irisin knockout mice. Our results highlight the potential of FNDC5/irisin to slow GACD, providing new insights and potential therapeutic strategies for the prevention and treatment of GACD. |
| format | Article |
| id | doaj-art-2fccc9fa4c7f4eeba03d101e7644b033 |
| institution | OA Journals |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-2fccc9fa4c7f4eeba03d101e7644b0332025-08-20T02:32:23ZengElsevierRedox Biology2213-23172025-07-018410368210.1016/j.redox.2025.103682Muscle-derived factor alleviated cognitive impairment caused by intestinal ischemia-reperfusionYafang Tan0Guo Mu1Feixiang Wang2Xin Fan3Chengjie Yang4Zuan Shi5Yiping Bai6Bingqing Xie7Xuan Yu8Jianguo Feng9Jing Jia10Xiaobin Wang11Ye Chen12Jun Zhou13Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, 646000, China; Department of Anesthesiology, Biejing Anzhen Nanchong Hospital of Capital Medical University & Nanchong Central Hospital, Nanchong, 634700, ChinaDepartment of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China; Department of Anesthesiology, Zigong Fourth People's Hospital, Zigong, 643000, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, 646000, ChinaDepartment of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, 646000, ChinaDepartment of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, 646000, ChinaDepartment of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, 646000, ChinaDepartment of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China; Department of Anesthesiology, Biejing Anzhen Nanchong Hospital of Capital Medical University & Nanchong Central Hospital, Nanchong, 634700, ChinaDepartment of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, 646000, ChinaLaboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China; Institute of Epigenetics and Brain Science, Southwest Medical University, Luzhou, 646000, ChinaDepartment of Anesthesiology, Zigong Fourth People's Hospital, Zigong, 643000, ChinaDepartment of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, 646000, ChinaDepartment of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, 646000, ChinaDepartment of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, 646000, ChinaAnesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, 646000, China; Department of Traditional Chinese Medicine, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China; Corresponding author. Department of Traditional Chinese Medicine, The Affiliated Hospital, Southwest Medical University, Luzhou, China.Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, 646000, China; Corresponding author. Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou,646000, China.Intestinal ischemia/reperfusion (II/R) is a common and grave clinical event, with high morbidity and mortality which can cause cerebral dysfunctions. There are no ideal prevention and treatment measures yet. The present study aimed to determine whether muscle-derived factors can alleviate gut-associated cerebral dysfunctions (GACD) following II/R. We measured the tibialis anterior muscle thickness and irisin levels in patients with and without cognitive dysfunction following cardiopulmonary bypass surgery, calculating the correlation between irisin and cognitive impairment. We found that this protective effect is related to muscle-derived irisin. To elucidate the role of irisin in improving GACD, we knocked out FNDC5 to deplete endogenous irisin and supplemented exogenous irisin. Mechanistic insights into irisin's effects on GACD were investigated using in vivo and in vitro models, incorporating techniques such as transmission electron microscopy, protein docking analysis, gene overexpression, and western blotting. FNDC5/irisin deficiency aggravated cognitive impairments, the pro-inflammation microglia activation, oxidative injury, inflammatory response, neuronal apoptosis and ferroptosis, while recombinant FNDC5/irisin reversed the above changes leading to neurostructural and cognition recovery. Mechanistically, thioredoxin-interacting protein (TXNIP) was activated in the II/R-related neuropathology and was deteriorated in FNDC5/irisin knockout mice. Our results highlight the potential of FNDC5/irisin to slow GACD, providing new insights and potential therapeutic strategies for the prevention and treatment of GACD.http://www.sciencedirect.com/science/article/pii/S2213231725001958MuscleIrisinIntestinal ischemia reperfusionCerebral dysfunctionsMicroglia |
| spellingShingle | Yafang Tan Guo Mu Feixiang Wang Xin Fan Chengjie Yang Zuan Shi Yiping Bai Bingqing Xie Xuan Yu Jianguo Feng Jing Jia Xiaobin Wang Ye Chen Jun Zhou Muscle-derived factor alleviated cognitive impairment caused by intestinal ischemia-reperfusion Redox Biology Muscle Irisin Intestinal ischemia reperfusion Cerebral dysfunctions Microglia |
| title | Muscle-derived factor alleviated cognitive impairment caused by intestinal ischemia-reperfusion |
| title_full | Muscle-derived factor alleviated cognitive impairment caused by intestinal ischemia-reperfusion |
| title_fullStr | Muscle-derived factor alleviated cognitive impairment caused by intestinal ischemia-reperfusion |
| title_full_unstemmed | Muscle-derived factor alleviated cognitive impairment caused by intestinal ischemia-reperfusion |
| title_short | Muscle-derived factor alleviated cognitive impairment caused by intestinal ischemia-reperfusion |
| title_sort | muscle derived factor alleviated cognitive impairment caused by intestinal ischemia reperfusion |
| topic | Muscle Irisin Intestinal ischemia reperfusion Cerebral dysfunctions Microglia |
| url | http://www.sciencedirect.com/science/article/pii/S2213231725001958 |
| work_keys_str_mv | AT yafangtan musclederivedfactoralleviatedcognitiveimpairmentcausedbyintestinalischemiareperfusion AT guomu musclederivedfactoralleviatedcognitiveimpairmentcausedbyintestinalischemiareperfusion AT feixiangwang musclederivedfactoralleviatedcognitiveimpairmentcausedbyintestinalischemiareperfusion AT xinfan musclederivedfactoralleviatedcognitiveimpairmentcausedbyintestinalischemiareperfusion AT chengjieyang musclederivedfactoralleviatedcognitiveimpairmentcausedbyintestinalischemiareperfusion AT zuanshi musclederivedfactoralleviatedcognitiveimpairmentcausedbyintestinalischemiareperfusion AT yipingbai musclederivedfactoralleviatedcognitiveimpairmentcausedbyintestinalischemiareperfusion AT bingqingxie musclederivedfactoralleviatedcognitiveimpairmentcausedbyintestinalischemiareperfusion AT xuanyu musclederivedfactoralleviatedcognitiveimpairmentcausedbyintestinalischemiareperfusion AT jianguofeng musclederivedfactoralleviatedcognitiveimpairmentcausedbyintestinalischemiareperfusion AT jingjia musclederivedfactoralleviatedcognitiveimpairmentcausedbyintestinalischemiareperfusion AT xiaobinwang musclederivedfactoralleviatedcognitiveimpairmentcausedbyintestinalischemiareperfusion AT yechen musclederivedfactoralleviatedcognitiveimpairmentcausedbyintestinalischemiareperfusion AT junzhou musclederivedfactoralleviatedcognitiveimpairmentcausedbyintestinalischemiareperfusion |