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.
Highlights
Urinary F2-isoprostanes are validated indices of human oxidative status, reflecting an overall generation of free radicals, among them reactive oxygen species (ROS) [1,2,3]
The observed correlations between the examined acylcarnitines are in agreement with the findings from the metabolomics studies [18, 19]
Examining the associations between fasting levels of F2isoprostanes and acylcarnitines, we find that beta coefficients are consistently positive for the associations with C2, C8, C10, and C12, whereas for C3, C4, and C5 the beta coefficients are negative (Table 2)
Summary
Urinary F2-isoprostanes are validated indices of human oxidative status, reflecting an overall generation of free radicals, among them reactive oxygen species (ROS) [1,2,3]. We hypothesized that fatty acid oxidation plays the predominant role in the connection between mitochondrial metabolism and urinary F2-isoprostane levels, because mitochondrial fatty acid oxidation (a) produces higher levels of ROS [10] and (b) largely accounts for the peripheral tissue oxidative metabolism [11]. This hypothesis builds upon the protective roles that the intensive mitochondrial metabolism, fatty acid. We demonstrated that fasting levels of nonesterified fatty acids, which are known to stimulate muscle fat oxidation, correlate directly with urinary F2-isoprostanes [17]. We explored these questions by examining both F2-isoprostane and acylcarnitine data from the Insulin Resistance Atherosclerosis Study (IRAS) multiethnic cohort
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
