Lipids in Liver Failure Syndromes: A Focus on Eicosanoids, Specialized Pro-Resolving Lipid Mediators and Lysophospholipids

Abstract

Lipids are organic compounds insoluble in water with a variety of metabolic and non-metabolic functions. They not only represent an efficient energy substrate but can also act as key inflammatory and anti-inflammatory molecules as part of a network of soluble mediators at the interface of metabolism and the immune system. The role of endogenous bioactive lipid mediators has been demonstrated in several inflammatory diseases (rheumatoid arthritis, inflammatory bowel disease, atherosclerosis, cancer). The liver is unique in providing balanced immunotolerance to the exposure of bacterial components from the gut transiting through the portal vein and the lymphatic system. This balance is abruptly deranged in liver failure syndromes such as acute liver failure and acute-on-chronic liver failure. In these syndromes, researchers have recently focused on bioactive lipid mediators by global metabonomic profiling and uncovered the pivotal role of these mediators in the immune dysfunction observed in liver failure syndromes explaining the high occurrence of sepsis and subsequent organ failure. Among endogenous bioactive lipids, the mechanistic actions of three classes (eicosanoids, pro-resolving lipid mediators and lysophospholipids) in the pathophysiological modulation of liver failure syndromes will be the topic of this narrative review. Furthermore, the therapeutic potential of lipid-immune pathways will be described.

TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis

“…Lastly, as cell membrane PE can be a source of substrates for eicosanoid biosynthesis 32 , and as hepatocyte-derived eicosanoids are implicated in NASH pathogenesis 33 , we measured a panel of eicosanoids in the WD-fed mouse livers. None of the 19 detected eicosanoid species had different levels in Tlcd1/2 DKO livers compared to controls (Supplementary Fig.…”

An untargeted serum and urine lipidomics research based on UPLC–MS revealed the lipid alterations on adjuvant‐induced arthritis rats

“…It has been reported that adrenic acid, an arachidonic acid‐derived metabolite, exerts a powerful anti‐inflammatory effect by inhibiting LTB4 production in neutrophils (Brouwers et al, 2020). Similarly, lipoxin A4 and lipoxin B4, derivatives of AA, have been reported to exert anti‐inflammatory effects by reducing neutrophil recruitment on inflammation sites as well as enhancing efferocytosis (Artru et al, 2022). Unlike eicosanoid pro‐inflammatory mediators, studies have found that ω ‐3 PUFAs such as docosahexaenoic acid and eicosapentaenoic acid oxygenated metabolites resolvin D1 and resolvin E1 are synthesized during the resolution phase of inflammatory exudates and have potent anti‐inflammatory and immunomodulatory effects (Serhan, 2014).…”

“…It has been reported that adrenic acid, an arachidonic acid-derived metabolite, exerts a powerful anti-inflammatory effect by inhibiting LTB4 production in neutrophils (Brouwers et al, 2020). Similarly, lipoxin A4 and lipoxin B4, derivatives of AA, have been reported to exert anti-inflammatory effects by reducing neutrophil recruitment on inflammation sites as well as enhancing efferocytosis (Artru et al, 2022). Unlike eicosanoid pro- (Burstein et al, 2011).…”

Lysophosphatidylcholines modulate immunoregulatory checkpoints in peripheral monocytes and are associated with mortality in people with acute liver failure

“…One of the crucial steps of this pathway is indeed performed by LPCAT3 53 , selectively activated by Interferongamma, which incorporates polyunsaturated fatty acids (PUFA)-CoA into phospholipids, using J o u r n a l P r e -p r o o f phosphatidylcholines and phosphatidylethanolamine as substrates. Indeed, the links between lipid metabolism and immune system are multiple and many lipid mediators have been studied in ferroptosis including specialized pro-resolving mediators that would be an interesting research focus in acute liver failure 54 .…”