F2-Isoprostanes Reflect Oxidative Stress Correlated With Lean Mass and Bone Density but Not Insulin Resistance

Abstract

Context:F2-isoprostanes (F2-isoPs) are biomarkers for oxidative stress in humans and have been shown to be elevated in obesity, cardiovascular disease, and diabetes. Therefore, F2-isoPs are often implicated in oxidative stress contributing to insulin resistance, although this has not been rigorously examined.Objective:To determine whether urinary F2-isoPs are predictive of insulin sensitivity and other clinical metabolic parameters.Participants:Sedentary, weight-stable, nondiabetic adults equilibrated on a standard isocaloric diet.Main Outcome Measures:Insulin sensitivity via hyperinsulinemic-euglycemic clamp, urinary F2-isoPs by gas chromatography-mass spectrometry, and body composition by dual-energy x-ray absorptiometry.Results:No correlation was found between 15-F2t-IsoP nor its major metabolite, 2,3-dinor-5,6-dihydro-15-F2t-IsoP, with insulin sensitivity, even after adjusting for age, race, sex, BMI, and smoking status. 15-F2t-IsoP was also not associated with body fat. However, there was a strong negative correlation between 15-F2t-IsoP and lean body mass (LBM; r = −0.46, P = 0.0001), bone mineral content (BMC; r = −0.58, P < 0.0001), bone mineral density (BMD; r = −0.65, P < 0.0001), and skeletal muscle protein 4-hydroxynonenal (4-HNE; r = −0.54, P = 0.0239), another marker of oxidative stress. 15-F2t-IsoP was also positively associated with circulating triglycerides and total cholesterol, and increased as a function of age.Conclusions:Urinary 15-F2t-IsoP and its major metabolite are not associated with insulin sensitivity, suggesting the lipid peroxidation process that produces F2-isoPs does not reflect oxidative stress reactions operative in insulin resistance. However, urinary F2-isoPs were negatively correlated with LBM, BMC, BMD, and muscle 4-HNE. Because lean and bone mass decline as a function of biological aging, F2-isoPs may reflect the oxidative stress operative in the aging process.

Butyrate Stimulates Histone H3 Acetylation, 8-Isoprostane Production, RANKL Expression, and Regulated Osteoprotegerin Expression/Secretion in MG-63 Osteoblastic Cells

“…It has been found that iso-PGE 2 but not iso-PGF 2 alpha had an inhibitory effect on the induction of alkaline phosphatase activity in MC3T3-E1 preosteoblasts [42]. Urinary F2-isoprostanes levels have been found to show a negative correlation with bone mineral content and bone mineral density [43]. It has been found that patients with diabetes, obesity, hypercholesterolemia, smokers, etc., have higher levels of urinary isoprostane [44].…”

Fatty Acids: An Insight into the Pathogenesis of Neurodegenerative Diseases and Therapeutic Potential

“…For instance, Elharram et al, (2017) and Raefsky et al, (2018) demonstrated that deuterium-reinforced PUFAs (D-PUFA) are more resistant to lipid peroxidation mediated by ROS in comparison with regular hydrogenated PUFAs [ 221 ] and that in mouse models of cognitive impairment, with AD-like biochemical and structural pathologies, treatment with D-PUFA for 18 weeks showed a strong effect in the hippocampus and cortex. An approximate 55% reduction of F2-isoprostanes [ 222 ], which are biomarkers for OS in humans and are elevated in obesity [ 223 ], was observed. Moreover, prostaglandin F2α was reduced [ 217 ] and this compound is associated with neuropsychiatric and neurologic disorders [ 224 ].…”

Impact of Dairy Intake on Plasma F2-IsoProstane Profiles in Overweight Subjects with Hyperinsulinemia: A Randomized Crossover Trial

“…Moreover, the Framingham cohort study showed that urinary inflammation and oxidative stress (total isoprostane) parameters were inversely associated with total protein and plant protein [ 28 ]. Further, a cross-sectional study on healthy youth with weight stable for three months and an isocaloric diet (50% carbohydrate, 30% fat, 20% protein), reported no association between urinary 15-F 2t -IsoP and basal carbohydrate and lipid oxidation rate [ 29 ]. Contrary to the current study, no differences were demonstrated in consumption of total energy, carbohydrate, protein and fat between different quartiles of F 2 -isoP in a cross-sectional study among postmenopausal women [ 30 ].…”