Phospholipases and Reactive Oxygen Species Derived Lipid Biomarkers in Healthy and Diseased Humans and Animals – A Focus on Lysophosphatidylcholine

Abstract

Phospholipids (PL) are converted into lipid biomarkers by the action of phospholipases and reactive oxygen species (ROS), which are activated or released under certain physiological and pathophysiological conditions. Therefore, the in vivo concentration of such lipid biomarkers [e.g., lysophospholipids (LPLs)] is altered in humans and animals under different conditions such as inflammation, stress, medication, and nutrition. LPLs are particularly interesting because they are known to possess pro- and anti-inflammatory properties and may be generated by two different pathways: either by the influence of phospholipase A2 or by different reactive oxygen species that are generated in significant amounts under inflammatory conditions. Both lead to the cleavage of unsaturated acyl residues. This review provides a short summary of the mechanisms by which lipid biomarkers are generated under in vitro and in vivo conditions. The focus will be on lysophosphatidylcholine (LPC) because usually, this is the LPL species which occurs in the highest concentration and is, thus, easily detectable by chromatographic and spectroscopic methods. Finally, the effects of lipid biomarkers as signaling molecules and their roles in different human and animal pathologies such as infertility, cancer, atherosclerosis, and aging will be shortly discussed.

Oral Lycopene Administration Attenuates Inflammation and Oxidative Stress by Regulating Plasma Lipids in Rats with Lipopolysaccharide-Induced Epididymitis

“…LPC (22:6) suppresses the synthesis of inflammatory mediators as a polyunsaturated acyl, to antagonize inflammation induced by saturated fatty acids. 32 Consistent with previous studies, LPC (14:0), as a saturated LPC, was positively correlated with the levels of cytokines IL-α, IL-β, TNF-α, IL-6 and MCP-1 and positively correlated with MDA, reflecting the degree of inflammatory damage. The previous study suggested that LPC (14:0) in preoperative plasma of patients with esophageal squamous cell carcinoma is a marker metabolite for evaluating the prognosis of patients.…”

“…At present, the evidence for LPC’s importance as the biomarker to inflammation and oxidative stress is further developed. 5 , 32 , 35 Moreover, LPC also has the benefit of being a marker of fertility in that, in contrast to proteins, it is a non-specific marker that may be useful in both human and animal sperm. 36 The lipid compounds identified in this study as potential biomarkers still require comprehensive studies to confirm their therapeutic applicability.…”

The lipidomes of C. elegans with mutations in asm-3/acid sphingomyelinase and hyl-2/ceramide synthase show distinct lipid profiles during aging

“…On the other hand, hyl-2 and daf-16 show increased LPC levels at younger and older ages. In humans, elevated levels of LPCs in circulating low density lipoprotiens (LDLs) are associated with disease [ 48 ], and elevated LPC levels are observed in stress conditions, particularly inflammatory disease [ 49 ].…”

Lysophosphatidylcholine: Potential Target for the Treatment of Chronic Pain

“…Lp-PLA2 can also hydrolyze oxidized phospholipids to generate LPC and oxidized fatty acids. LPC is usually present in very small concentrations because of LPC catabolism through different pathways mediated by separate enzymes: (1) after synthesized, LPC is secreted outside the cell and hydrolyzed to lysophosphatidic acid (LPA) and choline by autotaxin (ATX) [ 31 ]; (2) LPC is converted back to PCs by the enzyme lysophosphatidylcholine acyltransferase (LPCAT) in the presence of Acyl-CoA [ 32 ]; (3) LPC molecules catalyzed by cytosolic lysophospholipase-transacylase (LPTA) to form PC and glycerophosphorylcholine (GPC) [ 33 ] ( Figure 1 ). The accumulation of LPC reflects increased PLA2-catalyzed PC hydrolysis or decreased LPC catabolism or a combination of both processes [ 34 ].…”