Bile acid metabolomics identifies chenodeoxycholic acid as a therapeutic agent for pancreatic necrosis.

acinar cells acute pancreatitis bile acids metabolomics chenodeoxycholic acid farnesoid X receptor obeticholic acid oxidative phosphorylation pancreatic necrosis

Journal

Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894

Informations de publication

Date de publication:
16 Nov 2023
Historique:
received: 27 02 2023
revised: 15 05 2023
accepted: 02 11 2023
medline: 1 12 2023
pubmed: 1 12 2023
entrez: 30 11 2023
Statut: aheadofprint

Résumé

Bile acids are altered and associated with prognosis in patients with acute pancreatitis (AP). Here, we conduct targeted metabolomic analyses to detect bile acids changes in patients during the acute (n = 326) and the recovery (n = 133) phases of AP, as well as in healthy controls (n = 60). Chenodeoxycholic acid (CDCA) decreases in the acute phase, increases in the recovery phase, and is associated with pancreatic necrosis. CDCA and its derivative obeticholic acid exhibit a protective effect against acinar cell injury in vitro and pancreatic necrosis in murine models, and RNA sequencing reveals that the oxidative phosphorylation pathway is mainly involved. Moreover, we find that overexpression of farnesoid X receptor (FXR, CDCA receptor) inhibits pancreatic necrosis, and interfering expression of FXR exhibits an opposite phenotype in mice. Our results possibly suggest that targeting CDCA is a potential strategy for the treatment of acinar cell necrosis in AP, but further verification is needed.

Identifiants

DOI: 10.1016/j.xcrm.2023.101304 PMID: 38035885
pubmed: 38035885
pii: S2666-3791(23)00498-6
doi: 10.1016/j.xcrm.2023.101304
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

101304

Informations de copyright

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

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Qingtian Zhu (Q)

Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.

Chenchen Yuan (C)

Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.

Xiaowu Dong (X)

Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.

Yaodong Wang (Y)

Department of Gastroenterology, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan, China.

Baiqiang Li (B)

Department of Critical Care Medicine, Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

Bo Tu (B)

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Weiwei Chen (W)

Department of Gastroenterology, Clinical Medical College, Yangzhou University, Yangzhou, China.

Xingmeng Xu (X)

Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.

Weijuan Gong (W)

Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.

Weiming Xiao (W)

Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.

Yanbing Ding (Y)

Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.

Lianghao Hu (L)

Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China. Electronic address: lianghao-hu@hotmail.com.

Weiqin Li (W)

Department of Critical Care Medicine, Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. Electronic address: liweiqindr@nju.edu.cn.

Guotao Lu (G)

Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China. Electronic address: gtlu@yzu.edu.cn.

Classifications MeSH