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

Cell Rep Med. 2023 Dec 19;4(12):101304. doi: 10.1016/j.xcrm.2023.101304. Epub 2023 Nov 29.

Abstract

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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Bile Acids and Salts*
  • Chenodeoxycholic Acid / pharmacology
  • Chenodeoxycholic Acid / therapeutic use
  • Humans
  • Mice
  • Pancreatitis, Acute Necrotizing* / drug therapy
  • Receptors, Cytoplasmic and Nuclear

Substances

  • Bile Acids and Salts
  • Receptors, Cytoplasmic and Nuclear
  • Chenodeoxycholic Acid