2. Academic Validation
  3. High-fat diet increases circulating palmitic acid produced by gut Bacteroides thetaiotaomicron to promote thrombosis

High-fat diet increases circulating palmitic acid produced by gut Bacteroides thetaiotaomicron to promote thrombosis

  • Cell Rep Med. 2025 Aug 19;6(8):102260. doi: 10.1016/j.xcrm.2025.102260.
Xiaoshan Huang 1,  Xiaopeng Tang 2,  Qiuyue He 3,  Dawit Adisu Tadese 1,  Kaixun Cao 2,  Jinai Gao 2,  Qiuyue Xu 3,  Ruomei Cheng 2,  Qiumin Lu 2,  Yifan Chen 1,  Min Yang 1,  Yan Du 3,  James Mwangi 1,  Heyu Ni 4,  Ren Lai 5
Affiliations

Affiliations

  • 1 KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), State Key Laboratory of Genetic Evolution & Animal Models, Sino-African Joint Research Center, New Cornerstone Science Laboratory, Kunming Institute of Zoology, the Chinese Academy of Sciences, No.17 Longxin Road, Kunming, Yunnan 650201, P.R. China; Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China.
  • 2 KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), State Key Laboratory of Genetic Evolution & Animal Models, Sino-African Joint Research Center, New Cornerstone Science Laboratory, Kunming Institute of Zoology, the Chinese Academy of Sciences, No.17 Longxin Road, Kunming, Yunnan 650201, P.R. China.
  • 3 Department of Clinical Laboratory, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
  • 4 Department of Laboratory Medicine and Pathobiology, Department of Medicine, and Department of Physiology, University of Toronto; Canadian Blood Services Centre for Innovation; St. Michael's Hospital, LKSKI-Keenan Research Centre, Toronto, ON M5B 1W8, Canada. Electronic address: heyu.ni@unityhealth.to.
  • 5 KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), State Key Laboratory of Genetic Evolution & Animal Models, Sino-African Joint Research Center, New Cornerstone Science Laboratory, Kunming Institute of Zoology, the Chinese Academy of Sciences, No.17 Longxin Road, Kunming, Yunnan 650201, P.R. China. Electronic address: rlai@mail.kiz.ac.cn.
PMID: 40749683 DOI: 10.1016/j.xcrm.2025.102260
Abstract

Circulating palmitic acid (PA) is generally considered to be provided from diets and endogenous synthesis and is adversely correlated with Cardiovascular Disease (CVD). It is unknown, however, if gut microbiota modulates circulating PA and potentiates CVD risk. Here we demonstrate that, in CVD patients, elevated circulating PA is accompanied with hypercoagulability and high gut Bacteroides thetaiotaomicron (BT) abundance. PA promotes coagulation by inhibiting a major endogenous anticoagulant activated protein C (APC) and enhancing platelet activation. Importantly, BT is capable of synthesizing PA, and high-fat diet amplifies gut BT colonization. Our findings show that BT transplantation elevates plasma PA and triggers hypercoagulation without alternating host lipogenesis. Hesperidin, a dietary flavonoid, inhibits PA-APC interaction to prevent hypercoagulation induced by PA or BT transplantation. Collectively, we reveal the promotion of high-fat diet on gut BT colonization that elevates circulating PA and CVD risk, suggesting an approach controlling CVD by targeting PA and BT.

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