ACSL5
Long-chain-fatty-acid--CoA ligase 5 (EC 6.2.1.3) (Arachidonate--CoA ligase) (EC 6.2.1.15) (Long-chain acyl-CoA synthetase 5) (LACS 5) [ACS5] [FACL5] [UNQ633/PRO1250]
Publications[править]
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
Keywords
- Ageing
- FXR
- Intestinal homeostasis
- Lipidomics
- Pla2G6
- XBP1