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

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.

• Authors: 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
• Journal: Cell metabolism (Cell Metab) Vol. 35 Issue 10 Pg. 1752-1766.e8 (10 03 2023) ISSN: 1932-7420 [Electronic] United States
• PMID: 37591244 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• hyodeoxycholic acid
• PPAR alpha
• Deoxycholic Acid
• Bile Acids and Salts

Topics

• Mice
• Animals
• Non-alcoholic Fatty Liver Disease (drug therapy, metabolism)
• PPAR alpha (metabolism)
• Liver (metabolism)
• Deoxycholic Acid (metabolism, therapeutic use)
• Bile Acids and Salts (metabolism)