2. Academic Validation
  3. Adipose Tissue-Resident Sphingomonas Paucimobilis Suppresses Adaptive Thermogenesis by Reducing 15-HETE Production and Inhibiting AMPK Pathway

Adipose Tissue-Resident Sphingomonas Paucimobilis Suppresses Adaptive Thermogenesis by Reducing 15-HETE Production and Inhibiting AMPK Pathway

  • Adv Sci (Weinh). 2024 Oct 30:e2310236. doi: 10.1002/advs.202310236.
Yucheng Zhu 1,  Ruiqi Yang 1,  Zhangchao Deng 1,  Bohua Deng 1,  Kun Zhao 2,  Chen Dai 3,  Gang Wei 4,  YanJiang Wang 5,  Jinshui Zheng 6,  Zhuqing Ren 1,  Wentao Lv 7,  Yingping Xiao 7,  Zhinan Mei 8,  Tongxing Song 1
Affiliations

Affiliations

  • 1 College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.
  • 2 Department of Endocrinology, the Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100700, China.
  • 3 Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 4 Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing, Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
  • 5 Beijing Chao-yang Hospital, Capital Medical University, Beijing, 100020, China.
  • 6 State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, 430070, China.
  • 7 State 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, China.
  • 8 College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.
PMID: 39476363 DOI: 10.1002/advs.202310236
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.

Keywords

15‐HETE; AMPK; adaptive thermogenesis; adipose tissues; chronic inflammation; microbes.

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