Adipose Tissue‐Resident Sphingomonas Paucimobilis Suppresses Adaptive Thermogenesis by Reducing 15‐HETE Production and Inhibiting AMPK Pathway
Abstract Obesity represents a low‐grade chronic inflammation status, which is associated with compromised adaptive thermogenesis. However, the mechanisms underlying the defective activation of thermogenesis in chronic inflammation remain unclear. Here, a chronic inflammatory model is first estabolis...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-12-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202310236 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850052995857776640 |
|---|---|
| author | Yucheng Zhu Ruiqi Yang Zhangchao Deng Bohua Deng Kun Zhao Chen Dai Gang Wei YanJiang Wang Jinshui Zheng Zhuqing Ren Wentao Lv Yingping Xiao Zhinan Mei Tongxing Song |
| author_facet | Yucheng Zhu Ruiqi Yang Zhangchao Deng Bohua Deng Kun Zhao Chen Dai Gang Wei YanJiang Wang Jinshui Zheng Zhuqing Ren Wentao Lv Yingping Xiao Zhinan Mei Tongxing Song |
| author_sort | Yucheng Zhu |
| collection | DOAJ |
| description | Abstract Obesity represents a low‐grade chronic inflammation status, which is associated with compromised adaptive thermogenesis. However, the mechanisms underlying the defective activation of thermogenesis in chronic inflammation remain unclear. Here, a chronic inflammatory model is first estabolished by injecting mice with low‐dose lipopolysaccharide (LPS) before cold exposure, and then it is verified that LPS treatment can decrease the core body temperature of mice and alter the microbial distribution in epididymal white adipose tissue (eWAT). An adipose tissue‐resident bacterium Sphingomonas paucimobilis is identified as a potential inhibitor on the activation of brown fat and browning of inguinal WAT, resulting in defective adaptive thermogenesis. Mechanically, LPS and S. paucimobilis inhibit the production and release of 15‐HETE by suppressing its main metabolic enzyme 12 lipoxygenase (12‐LOX) and 15‐ Hydroxyeicosatetraenoic acid (15‐HETE) rescues the impaired thermogenesis. Interestingly, 15‐HETE directly binds to AMP‐activated protein kinase α (AMPKα) and elevates the phosphorylation of AMPK, leading to the activation of uncoupling protein 1 (UCP1) and mitochondrial oxidative phosphorylation (OXPHOS) complexes. Further analysis with human obesity subjects reveals that individuals with high body mass index displayed lower 15‐HETE levels. Taken together, this work improves the understanding of how chronic inflammation impairs adaptive thermogenesis and provides novel targets for alleviating obesity. |
| format | Article |
| id | doaj-art-0237eeaeb73a4fc7bf2c22f3b88845e8 |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-0237eeaeb73a4fc7bf2c22f3b88845e82025-08-20T02:52:41ZengWileyAdvanced Science2198-38442024-12-011147n/an/a10.1002/advs.202310236Adipose Tissue‐Resident Sphingomonas Paucimobilis Suppresses Adaptive Thermogenesis by Reducing 15‐HETE Production and Inhibiting AMPK PathwayYucheng Zhu0Ruiqi Yang1Zhangchao Deng2Bohua Deng3Kun Zhao4Chen Dai5Gang Wei6YanJiang Wang7Jinshui Zheng8Zhuqing Ren9Wentao Lv10Yingping Xiao11Zhinan Mei12Tongxing Song13College of Animal Science and Technology Huazhong Agricultural University Wuhan 430070 ChinaCollege of Animal Science and Technology Huazhong Agricultural University Wuhan 430070 ChinaCollege of Animal Science and Technology Huazhong Agricultural University Wuhan 430070 ChinaCollege of Animal Science and Technology Huazhong Agricultural University Wuhan 430070 ChinaDepartment of Endocrinology the Seventh Medical Center of Chinese PLA General Hospital Beijing 100700 ChinaInstitute of Organ Transplantation Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 ChinaBeijing Key Laboratory of Diabetes Research and Care Department of Endocrinology, Beijing Diabetes Institute Beijing Tongren Hospital Capital Medical University Beijing 100730 ChinaBeijing Chao‐yang Hospital Capital Medical University Beijing 100020 ChinaState Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan 430070 ChinaCollege of Animal Science and Technology Huazhong Agricultural University Wuhan 430070 ChinaState Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro‐Products Institute of Agro‐Product Safety and Nutrition Zhejiang Academy of Agricultural Sciences Hangzhou 310021 ChinaState Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro‐Products Institute of Agro‐Product Safety and Nutrition Zhejiang Academy of Agricultural Sciences Hangzhou 310021 ChinaCollege of Plant Science and Technology Huazhong Agricultural University Wuhan 430070 ChinaCollege of Animal Science and Technology Huazhong Agricultural University Wuhan 430070 ChinaAbstract Obesity represents a low‐grade chronic inflammation status, which is associated with compromised adaptive thermogenesis. However, the mechanisms underlying the defective activation of thermogenesis in chronic inflammation remain unclear. Here, a chronic inflammatory model is first estabolished by injecting mice with low‐dose lipopolysaccharide (LPS) before cold exposure, and then it is verified that LPS treatment can decrease the core body temperature of mice and alter the microbial distribution in epididymal white adipose tissue (eWAT). An adipose tissue‐resident bacterium Sphingomonas paucimobilis is identified as a potential inhibitor on the activation of brown fat and browning of inguinal WAT, resulting in defective adaptive thermogenesis. Mechanically, LPS and S. paucimobilis inhibit the production and release of 15‐HETE by suppressing its main metabolic enzyme 12 lipoxygenase (12‐LOX) and 15‐ Hydroxyeicosatetraenoic acid (15‐HETE) rescues the impaired thermogenesis. Interestingly, 15‐HETE directly binds to AMP‐activated protein kinase α (AMPKα) and elevates the phosphorylation of AMPK, leading to the activation of uncoupling protein 1 (UCP1) and mitochondrial oxidative phosphorylation (OXPHOS) complexes. Further analysis with human obesity subjects reveals that individuals with high body mass index displayed lower 15‐HETE levels. Taken together, this work improves the understanding of how chronic inflammation impairs adaptive thermogenesis and provides novel targets for alleviating obesity.https://doi.org/10.1002/advs.20231023615‐HETEadaptive thermogenesisadipose tissuesAMPKchronic inflammationmicrobes |
| spellingShingle | Yucheng Zhu Ruiqi Yang Zhangchao Deng Bohua Deng Kun Zhao Chen Dai Gang Wei YanJiang Wang Jinshui Zheng Zhuqing Ren Wentao Lv Yingping Xiao Zhinan Mei Tongxing Song Adipose Tissue‐Resident Sphingomonas Paucimobilis Suppresses Adaptive Thermogenesis by Reducing 15‐HETE Production and Inhibiting AMPK Pathway Advanced Science 15‐HETE adaptive thermogenesis adipose tissues AMPK chronic inflammation microbes |
| title | Adipose Tissue‐Resident Sphingomonas Paucimobilis Suppresses Adaptive Thermogenesis by Reducing 15‐HETE Production and Inhibiting AMPK Pathway |
| title_full | Adipose Tissue‐Resident Sphingomonas Paucimobilis Suppresses Adaptive Thermogenesis by Reducing 15‐HETE Production and Inhibiting AMPK Pathway |
| title_fullStr | Adipose Tissue‐Resident Sphingomonas Paucimobilis Suppresses Adaptive Thermogenesis by Reducing 15‐HETE Production and Inhibiting AMPK Pathway |
| title_full_unstemmed | Adipose Tissue‐Resident Sphingomonas Paucimobilis Suppresses Adaptive Thermogenesis by Reducing 15‐HETE Production and Inhibiting AMPK Pathway |
| title_short | Adipose Tissue‐Resident Sphingomonas Paucimobilis Suppresses Adaptive Thermogenesis by Reducing 15‐HETE Production and Inhibiting AMPK Pathway |
| title_sort | adipose tissue resident sphingomonas paucimobilis suppresses adaptive thermogenesis by reducing 15 hete production and inhibiting ampk pathway |
| topic | 15‐HETE adaptive thermogenesis adipose tissues AMPK chronic inflammation microbes |
| url | https://doi.org/10.1002/advs.202310236 |
| work_keys_str_mv | AT yuchengzhu adiposetissueresidentsphingomonaspaucimobilissuppressesadaptivethermogenesisbyreducing15heteproductionandinhibitingampkpathway AT ruiqiyang adiposetissueresidentsphingomonaspaucimobilissuppressesadaptivethermogenesisbyreducing15heteproductionandinhibitingampkpathway AT zhangchaodeng adiposetissueresidentsphingomonaspaucimobilissuppressesadaptivethermogenesisbyreducing15heteproductionandinhibitingampkpathway AT bohuadeng adiposetissueresidentsphingomonaspaucimobilissuppressesadaptivethermogenesisbyreducing15heteproductionandinhibitingampkpathway AT kunzhao adiposetissueresidentsphingomonaspaucimobilissuppressesadaptivethermogenesisbyreducing15heteproductionandinhibitingampkpathway AT chendai adiposetissueresidentsphingomonaspaucimobilissuppressesadaptivethermogenesisbyreducing15heteproductionandinhibitingampkpathway AT gangwei adiposetissueresidentsphingomonaspaucimobilissuppressesadaptivethermogenesisbyreducing15heteproductionandinhibitingampkpathway AT yanjiangwang adiposetissueresidentsphingomonaspaucimobilissuppressesadaptivethermogenesisbyreducing15heteproductionandinhibitingampkpathway AT jinshuizheng adiposetissueresidentsphingomonaspaucimobilissuppressesadaptivethermogenesisbyreducing15heteproductionandinhibitingampkpathway AT zhuqingren adiposetissueresidentsphingomonaspaucimobilissuppressesadaptivethermogenesisbyreducing15heteproductionandinhibitingampkpathway AT wentaolv adiposetissueresidentsphingomonaspaucimobilissuppressesadaptivethermogenesisbyreducing15heteproductionandinhibitingampkpathway AT yingpingxiao adiposetissueresidentsphingomonaspaucimobilissuppressesadaptivethermogenesisbyreducing15heteproductionandinhibitingampkpathway AT zhinanmei adiposetissueresidentsphingomonaspaucimobilissuppressesadaptivethermogenesisbyreducing15heteproductionandinhibitingampkpathway AT tongxingsong adiposetissueresidentsphingomonaspaucimobilissuppressesadaptivethermogenesisbyreducing15heteproductionandinhibitingampkpathway |