Fig. 2
From: Fatty acids role in multiple sclerosis as “metabokines”
FAs and FA metabolism modulate immune cells’ differentiation and function in MS. a Intracellular FA composition is related to Th17 pathogenicity as the CD5L-prompted rise of unsaturated FA proportion facilitate the maintenance of a non-pathogenic state. b Intracellular FA metabolic pattern witnesses a significant difference among CD4+T helper cells which facilitates their diverged differentiation. FA synthesis (FAS) initiated by ACC1 favors the differentiation towards pathogenic Th17, while FA metabolism indispensable of CPT1/2 induces the differentiation towards protective Treg. Extracellular SCFA, LCFA, and PUFA as metabokines manifest broad immunomodulatory property (c–e). c SCFAs, by manipulating protein acetylation and inner metabolic state, enhance Treg differentiation, and transform various innate immune cells into a more protective state and, meanwhile, reduce the number and function of Th17 and Th1 cells. Interestingly, SCFAs regulate B lymphocytes function in a dose-dependent manner. d Adipose-resident oleic acid, as a kind of LCFA, increases FA oxidation (FAO) of Treg, leading to a boost of its regulative function. e PUFAs, especially omega-3 DHA, induce the CD4+T naïve cells differentiation into Treg while dampening proinflammatory cytokine secretion of Th17, Th1 cells. Omega-3 PUFAs also exhibit modulatory role for innate immune cells, favoring the resolution of inflammation. MAC macrophage, MAST mast cell, NEUT neutrophil