Atherogenic lipidomics profile in healthy individuals with low cardiorespiratory fitness: The HUNT3 fitness study
Markus Nodeland, Marie Klevjer, Julie Caroline Sæther, Guro F. Giskeødegård, Tone F. Bathen, Ulrik Wisløff, Anja Bye
Abstract
Background and aims Low cardiorespiratory fitness is a strong and independent risk factor for cardiovascular disease (CVD). Serum profiling of healthy individuals with large differences in cardiorespiratory fitness may therefore reveal early biomarkers of CVD development. Thus, we aimed to identify circulating lipoprotein subfractions differentially expressed between groups of individuals with large differences in cardiorespiratory fitness, measured as maximal oxygen uptake (VO 2max ). Methods Healthy subjects (40–59 years) were selected from the third wave of the Trøndelag health study (HUNT3) based on having an age-dependent high VO 2max (47.1 ± 7.7 mL kg −1 ·min −1 , n = 103) or low VO 2max (31.4 ± 4.9 mL kg −1 ·min −1 , n = 108). The individuals were matched on gender, age, physical activity level and fasting status. Results 99 lipoprotein subfractions were quantified in serum samples using nuclear magnetic resonance (NMR) lipidomics. Standard clinical analyses showed similar levels of total cholesterol, low-density lipoprotein (LDL)-cholesterol and high-density lipoprotein (HDL)-cholesterol between the groups, and slightly higher levels of triglycerides in participants with low VO 2max . Thirteen lipoprotein subfractions were increased in the low VO 2max group compared to the high VO 2max group ( p < 0.005), including mainly large very low-density lipoprotein (VLDL) subfractions. In addition, triglyceride levels in small-sized HDL and LDL particles were increased in participants with low VO 2max . Correlation analyses between VO 2max and lipoproteins subfractions displayed a negative correlation between VO 2max and the levels of cholesterol and phospholipids in the small HDL particles. The lipoprotein profile of individuals with low VO 2max is similar to the profile of insulin resistant individuals. Conclusions Low VO 2max was associated with enrichment of large VLDL particles, as well as an increased triglycerides content in the small and dense HDL and LDL particles. This unfavorable lipid profile is likely to be involved in the strong associations between VO 2max and CVD.