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Long-chain-fatty-acid--CoA ligase 5 (EC (Arachidonate--CoA ligase) (EC (Long-chain acyl-CoA synthetase 5) (LACS 5) [ACS5] [FACL5] [UNQ633/PRO1250]


Ageing sensitized by iPLA β deficiency induces liver fibrosis and intestinal atrophy involving suppression of homeostatic genes and alteration of intestinal lipids and bile acids.

Ageing is a major risk factor for various forms of liver and gastrointestinal (GI) disease and genetic background may contribute to the pathogenesis of these diseases. Group VIA phospholipase A2 or iPLA β is a homeostatic PLA by playing a role in phospholipid metabolism and remodeling. Global iPLA β mice exhibit aged-dependent phenotypes with body weight loss and abnormalities in the bone and brain. We have previously reported the abnormalities in these mutant mice showing susceptibility for chemical-induced liver injury and colitis. We hypothesize that iPLA β deficiency may sensitize with ageing for an induction of GI injury. Male wild-type and iPLA β mice at 4 and 20-22months of age were studied. Aged, but not young, iPLA β mice showed increased hepatic fibrosis and biliary ductular expansion as well as severe intestinal atrophy associated with increased apoptosis, pro-inflammation, disrupted tight junction, and reduced number of mucin-containing globlet cells. This damage was associated with decreased expression of intestinal endoplasmic stress XBP1 and its regulator HNF1α, FATP4, ACSL5, bile-acid transport genes as well as nuclear receptors LXRα and FXR. By LC/MS-MS profiling, iPLA β deficiency in aged mice caused an increase of intestinal arachidonate-containing phospholipids concomitant with a decrease in ceramides. By the suppression of intestinal FXR/FGF-15 signaling, hepatic bile-acid synthesis gene expression was increased leading to an elevation of secondary and hydrophobic bile acids in liver, bile, and intestine. In conclusions, ageing sensitized by iPLA β deficiency caused a decline of key intestinal homeostatic genes resulting in the development of GI disease in a gut-to-liver manner.

MeSH Terms

  • Aging
  • Animals
  • Bile Acids and Salts
  • Ceramides
  • Group VI Phospholipases A2
  • Intestinal Diseases
  • Liver Cirrhosis
  • Mice
  • Mice, Knockout
  • Phospholipids


  • Ageing
  • FXR
  • Intestinal homeostasis
  • Lipidomics
  • Pla2G6
  • XBP1