Lipid Mediators and Metabolic Inflammation: From Molecular Mechanisms to a New Therapeutic Paradigm

Chronic low-grade inflammation is a common pathogenetic mechanism of metabolic, cardiovascular, renal, hepatic, and neurodegenerative diseases. This essay critically analyzes the role of lipid mediators in the pathogenesis of chronic inflammation and substantiates the thesis that the key factor in the transition from acute to chronic inflammation is not the excessive production of pro-inflammatory mediators, but the insufficiency of pro-resolution pathways. The molecular mechanisms of metabolic reprogramming of immune cells are reviewed, in particular, the switching of macrophages between glycolytic (M1) and oxidative (M2) phenotypes, the role of CD36 and FATP2 in lipotoxicity, impaired β-oxidation of fatty acids, and the accumulation of toxic lipid intermediates (free cholesterol, ceramides, lactate, succinate). The dual nature of lipid mediators is analyzed – from pro-inflammatory eicosanoids (LTB4, PGE2) to specialized pro-resolution mediators (SPMs), including lipoxins, resolvins, protectins and maresins. Data on the imbalance between pro-inflammatory and pro-resolution mediators in atherosclerosis, metabolic syndrome, diabetes mellitus, chronic kidney disease, non-alcoholic steatohepatitis, neurodegenerative and autoimmune diseases are presented. Special attention is paid to the concept of “unalamation”, which radically rethinks the etiology of chronic inflammation. A therapeutic paradigm based on the stimulation of endogenous pro-resolution pathways (SPMs and their synthetic analogues) is substantiated as an alternative to traditional anti-inflammatory therapy that inhibits pro-inflammatory mediators. The limitations of existing research, controversies, and prospects for further scientific exploration in this field are discussed.