2. Academic Validation
  3. Adipocyte FMO3-derived TMAO induces WAT dysfunction and metabolic disorders by promoting inflammasome activation in ageing

Adipocyte FMO3-derived TMAO induces WAT dysfunction and metabolic disorders by promoting inflammasome activation in ageing

  • Nat Commun. 2025 Oct 6;16(1):8873. doi: 10.1038/s41467-025-63905-1.
Thashma Ganapathy # 1,  Juntao Yuan # 1,  Melody Yuen-Man Ho 1,  Kelvin Ka-Lok Wu 1,  Md Moinul Hoque 1,  Baomin Wang 2,  Xiaomu Li 2,  Kai Wang 1,  Martin Wabitsch 3,  Xuejia Feng 4 5,  Yongxia Niu 4 5,  Kekao Long 1,  Qizhou Lian 4 5 6 7,  Yuyan Zhu 8,  Kenneth King-Yip Cheng 9 10
Affiliations

Affiliations

  • 1 Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, China.
  • 2 Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China.
  • 3 Division of Paediatric Endocrinology and Diabetes Department of Paediatrics and Adolescent Medicine University Medical Center Ulm, German Center for Child and Adolescent Health, Ulm, Germany.
  • 4 Faculty of Synthetic Biology, Shenzhen University of Advanced Technology, Shenzhen, China.
  • 5 Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • 6 Prenatal Diagnostic Center and Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • 7 Center for Translational Stem Cell Biology, Hong Kong, China; HKUMed Laboratory of Cellular Therapeutics, University of Hong Kong, Hong Kong, China.
  • 8 Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hong Kong, China.
  • 9 Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, China. kenneth.ky.cheng@polyu.edu.hk.
  • 10 Shenzhen Research Institute, The Hong Kong Polytechnic University, Hong Kong, China. kenneth.ky.cheng@polyu.edu.hk.
  • # Contributed equally.
PMID: 41053195 DOI: 10.1038/s41467-025-63905-1
Abstract

Trimethylamine N-oxide (TMAO) contributes to cardio-metabolic diseases, with hepatic flavin-containing monooxygenase 3 (FMO3) recognized as its primary source. Here we demonstrate that elevated adipocyte FMO3 and its derived TMAO trigger white adipose tissue (WAT) dysfunction and its related metabolic disorders in ageing. In adipocytes, ageing or p53 activation upregulates FMO3 and TMAO levels. Adipocyte-specific ablation of FMO3 attenuates TMAO accumulation in WAT and circulation, leading to enhanced glucose metabolism and energy and lipid homeostasis in ageing and obese mice. These improvements are associated with reduced senescence, fibrosis and inflammation in WAT. Proteomics analysis identified TMAO-interacting proteins involved in inflammasome activation in adipocytes and macrophages. Mechanistically, TMAO binds to the central inflammasome adaptor protein ASC, promoting Caspase-1 activation and interleukin-1β production. Our findings uncover a pivotal role for adipocyte FMO3 in modulating TMAO production and WAT dysfunction by promoting inflammasome activation in ageing via an autocrine and paracrine manner.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z