2. Academic Validation
  3. Hyodeoxycholic acid alleviates non-alcoholic fatty liver disease through modulating the gut-liver axis

Hyodeoxycholic acid alleviates non-alcoholic fatty liver disease through modulating the gut-liver axis

  • Cell Metab. 2023 Aug 9;S1550-4131(23)00270-X. doi: 10.1016/j.cmet.2023.07.011.
Junliang Kuang 1,  Jieyi Wang 1,  Yitao Li 2,  Mengci Li 1,  Mingliang Zhao 1,  Kun Ge 1,  Dan Zheng 1,  Kenneth C P Cheung 2,  Boya Liao 2,  Shouli Wang 1,  Tianlu Chen 1,  Yinan Zhang 1,  Congrong Wang 3,  Guang Ji 4,  Peng Chen 5,  Hongwei Zhou 6,  Cen Xie 7,  Aihua Zhao 1,  Weiping Jia 8,  Xiaojiao Zheng 9,  Wei Jia 10
Affiliations

Affiliations

  • 1 Center for Translational Medicine, Shanghai Key Laboratory of Diabetes Mellitus and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
  • 2 School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
  • 3 Department of Endocrinology & Metabolism, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China.
  • 4 Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
  • 5 Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
  • 6 Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510655, China.
  • 7 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • 8 Center for Translational Medicine, Shanghai Key Laboratory of Diabetes Mellitus and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China. Electronic address: wpjia@sjtu.edu.cn.
  • 9 Center for Translational Medicine, Shanghai Key Laboratory of Diabetes Mellitus and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China. Electronic address: joyzheng99@sjtu.edu.cn.
  • 10 Center for Translational Medicine, Shanghai Key Laboratory of Diabetes Mellitus and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China. Electronic address: weijia1@hkbu.edu.hk.
PMID: 37591244 DOI: 10.1016/j.cmet.2023.07.011
Abstract

Non-alcoholic fatty liver disease (NAFLD) is regarded as a pandemic that affects about a quarter of the global population. Recently, host-gut microbiota metabolic interactions have emerged as distinct mechanistic pathways implicated in the development of NAFLD. Here, we report that a group of gut microbiota-modified bile acids (BAs), hyodeoxycholic acid (HDCA) species, are negatively correlated with the presence and severity of NAFLD. HDCA treatment has been shown to alleviate NAFLD in multiple mouse models by inhibiting intestinal farnesoid X receptor (FXR) and upregulating hepatic CYP7B1. Additionally, HDCA significantly increased abundances of probiotic species such as Parabacteroides distasonis, which enhances lipid catabolism through fatty acid-hepatic Peroxisome Proliferator-activated Receptor alpha (PPARα) signaling, which in turn upregulates hepatic FXR. These findings suggest that HDCA has therapeutic potential for treating NAFLD, with a unique mechanism of simultaneously activating hepatic CYP7B1 and PPARα.

Keywords

CYP7B1; NAFLD; PPARα; Parabacteroides distasonis; bile acid; farnesoid X receptor; hyodeoxycholic acid.

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