Omega‐3 carboxylic acids and fenofibrate differentially alter plasma lipid mediators in patients with non‐alcoholic fatty liver disease

Abstract

Fibrates and omega-3 polyunsaturated acids are used for the treatment of hypertriglyceridemia but have not demonstrated consistent effects on cardiovascular (CV) risk. In this study, we investigate how these two pharmacological agents influence plasma levels of bioactive lipid mediators, aiming to explore their efficacy beyond that of lipid-lowering agents. Plasma from overweight patients with nonalcoholic fatty liver disease (NAFLD) and hypertriglyceridemia, participating in a randomized placebo-controlled study investigating the effects of 12 weeks treatment with fenofibrate or omega-3 free carboxylic acids (OM-3CA) (200 mg or 4 g per day, respectively), were analyzed for eicosanoids and related PUFA species, N-acylethanolamines (NAE) and ceramides. OM-3CA reduced plasma concentrations of proinflammatory PGE 2 , as well as PGE 1 , PGD 1 and thromboxane B2 but increased prostacyclin, and eicosapentaenoic acid-and docosahexaenoic acid-derived lipids of lipoxygenase and cytochrome P450 monooxygenase (CYP) (e.g.,19,. Fenofibrate reduced plasma concentrations of vasoactive CYP-derived eicosanoids (DHETs). Although OM-3CA

Gut-derived short-chain fatty acids modulate skin barrier integrity by promoting keratinocyte metabolism and differentiation

“…For data acquisition and instrument control and for integration and quantification MassLynx software and TargetLynx software (Waters, UK) were used, respectively. Ceramide identification was confirmed through retention times and characteristic fragmentation patterns 87 . Relative quantification was performed using deuterated internal standards.…”

Management of metabolic-associated fatty liver disease: The diabetology perspective

“…Therefore, statin therapy should be considered in all patients, including those with compensated cirrhosis, except when the transaminase levels are > 3 times the upper limit of normal[ 60 ]. Although Omega-3 fatty acids and fenofibrate were found to offer potential benefits in patients with hypertriglyceridemia and MAFLD in a recent small clinical trial[ 62 ], firm conclusions cannot be reached without large-scale studies. Pro-protein convertase subtilisin/kexin type 9 inhibitors are used to treat hypercholesterolemia in patients with statin intolerance or in those unable to achieve target reduction of LDL-C with tolerated doses of statins.…”

Post-resolution macrophage-derived lipids shapes long-term tissue immunity and integrity

“…Prostanoids and hydroxy fatty acids were extracted from whole lung tissue as described (20,21). Briefly, lung tissue was homogenised in methanol, then diluted in water to a final concentration of 15 % (v/v) methanol/water.…”