Association between F₂-Isoprostane Metabolites and Weight Change in Older Women: A Longitudinal Analysis

Introduction: Theoretically, some metabolic traits may predispose older individuals to weight loss during aging, leading to increased all-cause mortality and many serious health issues. Biomarkers to robustly predict progressive weight loss during aging are, however, lacking. We prospectively assessed if urinary levels of F-2-isoprostanes and their peroxisomal beta-oxidation metabolite, 2,3-dinor-5,6-dihydro-15-F-2t-isoprostane (F-2-IsoP-M), were associated with subsequent weight loss in middle-aged and older women. Methods: Included in the analysis were 2,066 women aged 40-70 years, a subset of a prospective cohort study. F-2-isoprostanes (F-2-IsoPs) and its beta-oxidation metabolite, F-2-IsoP-M, were measured in urine using gas chromatography-mass spectrometry. Measurements of anthropometry and exposures to major determinants of body weight were performed at baseline and repeated thrice over 15-year follow-up. The longitudinal associations of F-2-IsoP-M and the F-2-IsoP-M to its parent compound, F-2-IsoP, ratio (MPR) with repeatedly measured weight changes were examined using linear mixed-effect models. Results: After adjusting for time-varying covariates: energy intake, physical activity, and comorbidity index, among others, levels of F-2-IsoP-M and the MPR were both inversely associated with percentage of weight change. Weight in the highest quartile of these two biomarkers was 1.33% (95% CI = -2.41, -0.24) and 1.09% (95% CI = -2.16, -0.02) lower than those in the lowest quartile group, with p for trend of 0.01 and 0.03, respectively. The inverse association was consistently seen across follow-up periods, although appearing stronger with prolonged follow-up. There was no association between the parent compound, F-2-IsoPs, and weight change. Conclusion: This study demonstrates the first piece of evidence to associate F-2-IsoP metabolism, peroxisomal beta-oxidation, with weight loss in older women. Further investigations into the role of lipid peroxidation and peroxisomal beta-oxidation in weight change among older individuals are warranted.