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

Junliang Kuang; Jieyi Wang; Yitao Li; Mengci Li; Mingliang Zhao; Kun Ge; Dan Zheng; Kenneth Chat Pan 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

doi:10.1016/j.cmet.2023.07.011

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

Junliang Kuang, Jieyi Wang, Yitao Li, Mengci Li, Mingliang Zhao, Kun Ge, Dan Zheng, Kenneth Chat Pan 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › peer-review

51 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1752-1766.e8
Number of pages	24
Journal	Cell Metabolism
Volume	35
Issue number	10
Early online date	16 Aug 2023
DOIs	https://doi.org/10.1016/j.cmet.2023.07.011
Publication status	Published - 3 Oct 2023

Scopus Subject Areas

Molecular Biology
Physiology
Cell Biology

User-Defined Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cmet.2023.07.011

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Kuang, J., Wang, J., Li, Y., Li, M., Zhao, M., Ge, K., Zheng, D., Cheung, K. C. P., Liao, B., Wang, S., Chen, T., Zhang, Y., Wang, C., Ji, G., Chen, P., Zhou, H., Xie, C., Zhao, A., Jia, W., ... Jia, W. (2023). Hyodeoxycholic acid alleviates non-alcoholic fatty liver disease through modulating the gut-liver axis. Cell Metabolism, 35(10), 1752-1766.e8. https://doi.org/10.1016/j.cmet.2023.07.011

@article{36d74dff13a74643b987386fda4c6a02,

title = "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.",

keywords = "bile acid, CYP7B1, farnesoid X receptor, hyodeoxycholic acid, NAFLD, Parabacteroides distasonis, PPARα",

author = "Junliang Kuang and Jieyi Wang and Yitao Li and Mengci Li and Mingliang Zhao and Kun Ge and Dan Zheng and Cheung, {Kenneth Chat Pan} and Boya Liao and Shouli Wang and Tianlu Chen and Yinan Zhang and Congrong Wang and Guang Ji and Peng Chen and Hongwei Zhou and Cen Xie and Aihua Zhao and Weiping Jia and Xiaojiao Zheng and Wei Jia",

note = "Funding Information: This work was supported by the National Key R&D Program of China ( 2022YFA0806400 , 2021YFA1301300 , and 2019YFA0802300 ), the National Natural Science Foundation of China ( 82270917 , 82122012 , 82170833 , and 82170601 ), the Science and Technology Committee of Shanghai Municipality Government ( 23YF1432000 ), and Shanghai Research Center for Endocrine and Metabolic Diseases (2022ZZ01002). Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = oct,

day = "3",

doi = "10.1016/j.cmet.2023.07.011",

language = "English",

volume = "35",

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journal = "Cell Metabolism",

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publisher = "Cell Press",

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Kuang, J, Wang, J, Li, Y, Li, M, Zhao, M, Ge, K, Zheng, D, Cheung, KCP, Liao, B, Wang, S, Chen, T, Zhang, Y, Wang, C, Ji, G, Chen, P, Zhou, H, Xie, C, Zhao, A, Jia, W, Zheng, X & Jia, W 2023, 'Hyodeoxycholic acid alleviates non-alcoholic fatty liver disease through modulating the gut-liver axis', Cell Metabolism, vol. 35, no. 10, pp. 1752-1766.e8. https://doi.org/10.1016/j.cmet.2023.07.011

TY - JOUR

T1 - Hyodeoxycholic acid alleviates non-alcoholic fatty liver disease through modulating the gut-liver axis

AU - Kuang, Junliang

AU - Wang, Jieyi

AU - Li, Yitao

AU - Li, Mengci

AU - Zhao, Mingliang

AU - Ge, Kun

AU - Zheng, Dan

AU - Cheung, Kenneth Chat Pan

AU - Liao, Boya

AU - Wang, Shouli

AU - Chen, Tianlu

AU - Zhang, Yinan

AU - Wang, Congrong

AU - Ji, Guang

AU - Chen, Peng

AU - Zhou, Hongwei

AU - Xie, Cen

AU - Zhao, Aihua

AU - Jia, Weiping

AU - Zheng, Xiaojiao

AU - Jia, Wei

N1 - Funding Information: This work was supported by the National Key R&D Program of China ( 2022YFA0806400 , 2021YFA1301300 , and 2019YFA0802300 ), the National Natural Science Foundation of China ( 82270917 , 82122012 , 82170833 , and 82170601 ), the Science and Technology Committee of Shanghai Municipality Government ( 23YF1432000 ), and Shanghai Research Center for Endocrine and Metabolic Diseases (2022ZZ01002). Publisher Copyright: © 2023 The Authors

PY - 2023/10/3

Y1 - 2023/10/3

N2 - 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.

AB - 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.

KW - bile acid

KW - CYP7B1

KW - farnesoid X receptor

KW - hyodeoxycholic acid

KW - NAFLD

KW - Parabacteroides distasonis

KW - PPARα

UR - http://www.scopus.com/inward/record.url?scp=85169801386&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2023.07.011

DO - 10.1016/j.cmet.2023.07.011

M3 - Journal article

SN - 1550-4131

VL - 35

SP - 1752-1766.e8

JO - Cell Metabolism

JF - Cell Metabolism

IS - 10

ER -

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

Abstract

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UN SDGs

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