Urinary F2-Isoprostanes and Metabolic Markers of Fat Oxidation

Abstract

Metabolomic studies of increased fat oxidation showed increase in circulating acylcarnitines C2, C8, C10, and C12 and decrease in C3, C4, and C5. We hypothesize that urinary F2-isoprostanes reflect intensity of fatty acid oxidation and are associated with circulating C2, C8, C10, and C12 directly and with C3, C4, and C5 inversely. Four urinary F2-isoprostane isomers and serum acylcarnitines are quantified using LC-MS/MS within the Insulin Resistance Atherosclerosis Study nondiabetic cohort (n= 682). Cross-sectional associations between fasting urinary F2-isoprostanes (summarized as a composite index) and the selected acylcarnitines are examined using generalized linear models. F2-isoprostane index is associated with C2 and C12 directly and with C5 inversely: the adjusted beta coefficients are 0.109, 0.072, and −0.094, respectively (P< 0.05). For these acylcarnitines and for F2-isoprostanes, the adjusted odds ratios (ORs) of incident diabetes are calculated from logistic regression models: the ORs (95% CI) are 0.77 (0.60–0.97), 0.79 (0.62–1.01), 1.18 (0.92–1.53), and 0.51 (0.35–0.76) for C2, C12, C5, and F2-isoprostanes, respectively. The direction of the associations between urinary F2-isoprostanes and three acylcarnitines (C2, C5, and C12) supports our hypothesis. The inverse associations of C2 and C12 and with incident diabetes are consistent with the suggested protective role of efficient fat oxidation.