Higher Plasma Saturated and Omega-6 Fatty Acids Associated with Cholesterol Homeostasis and Gut Microbiota in Pediatric Type 2 Diabetes and Metabolic Syndrome.

Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) in children and adolescents are characterized by altered lipid metabolism and gut microbiota. Prior untargeted (nonquantitative) lipidomics of the present T2DM and MetS pediatric cohort revealed alterations in plasma lipids. Fatty acids (FAs) bonded to plasma phospholipids (PLs) and cholesterol esters (CEs) reflect endogenous metabolism and exogenous sources. The present study focused on targeted quantification of FAs esterified to plasma PLs and CEs in children and adolescents with T2DM and MetS and healthy controls (n = 60, ages 7 to 17). Regression models and Spearman correlations assessed associations of esterified FA with the disease, metabolic risk factors, pro-inflammatory cytokines, and gut microbiota composition. T2DM and MetS groups featured higher concentrations of saturated FAs esterified to PLs (C17:0) and CEs (C10:0, C12:0, and C24:0) than healthy controls. Also, both groups had higher omega-6 FA levels, including dihomo-γ-linolenic acid (C20:3n-6) in both plasma fractions (PLs and CEs), C22:5n-6 in PLs, and C18:2n-6 and C20:4n-6 in CEs. These FAs were inversely correlated with high-density lipoprotein cholesterol and directly correlated with obesity, triglycerides, and insulin resistance. Also, MetS had a high CE-omega-6/omega-3 ratio. Gut microbial taxa associated with T2DM and MetS after Tanner, sex, and body mass index percentile adjustment were Agathobacter, Dorea, Fusicatenibacter, and Gemmiger, with higher abundances than those in healthy controls, and the genus Faecalimonas at lower abundances. This work contributes to the current knowledge of lipid metabolism and the role of gut microbiota in T2DM and MetS in children and adolescents.