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

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机构： [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

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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.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

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出版当年[2022]版：

大类 | 1 区

生物学

小类 | 1 区细胞生物学 1 区内分泌学与代谢

最新[2025]版：

大类 | 1 区

生物学

小类 | 1 区细胞生物学 1 区内分泌学与代谢

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出版当年[2021]版：

Q1 CELL BIOLOGY Q1 ENDOCRINOLOGY & METABOLISM

最新[2023]版：

Q1 CELL BIOLOGY Q1 ENDOCRINOLOGY & METABOLISM

影响因子： 27.7 最新[2023版] 31.2 最新五年平均 31.373 出版当年[2021版] 35.104 出版当年五年平均 27.287 出版前一年[2020版] 29 出版后一年[2022版]

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第一作者机构： [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

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通讯机构： [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

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