小柯机器人

上海交通大学医学院附属上海第六人民医院贾伟、郑晓皎和贾伟平研究组发现，羟基脱氧胆酸(HDCA)通过调节肠-肝轴减轻非酒精性脂肪性肝病(NAFLD)。2023年8月16日，国际知名学术期刊《细胞—代谢》发表了这一成果。

他们报告了一组肠道微生物群修饰的胆汁酸(BAs)、HDCA分子，与NAFLD的存在和严重程度呈负相关。在多种小鼠模型中，HDCA治疗已被证明可以通过抑制肠道法尼松X受体(FXR)和上调肝脏CYP7B1来缓解NAFLD。此外，HDCA显著增加了异裂副杆菌等益生菌的丰度，通过脂肪酸-肝脏过氧化物酶体增殖物激活受体α (PPARα)信号通路促进脂质分解代谢，进而上调肝脏FXR。

这些发现表明，HDCA具有同时激活肝脏CYP7B1和PPARα的独特机制，具有治疗NAFLD的治疗潜力。

研究人员表示，NAFLD被认为是一种影响全球约四分之一人口的流行病。最近，宿主-肠道微生物群代谢相互作用已成为NAFLD发展中涉及的独特机制途径。

附：英文原文

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

Author: Junliang Kuang, Jieyi Wang, Yitao Li, Mengci Li, Mingliang Zhao, Kun Ge, Dan Zheng, Kenneth C.P. Cheung, Boya Liao, Shouli Wang, Tianlu Chen, Yinan Zhang, Congrong Wang, Guang Ji, Peng Chen, Hongwei Zhou, Cen Xie, Aihua Zhao, Weiping Jia, Xiaojiao Zheng, Wei Jia

Issue&Volume: 2023-08-16

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.

DOI: 10.1016/j.cmet.2023.07.011

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00270-X

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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