Changes in plasma levels of a selected panel of miRNAs do not explain the shift from cholesterol-synthesizer to cholesterol-absorber phenotype in men with abdominal obesity after diet-induced weight loss.

Abstract

Individuals with overweight or obesity exhibit a cholesterol-synthesizer phenotype (high plasma lathosterol/campesterol ratio). Previously, we have reported that weight loss in men with abdominal obesity shifted this phenotype towards a cholesterol-absorber (low plasma ratio) profile. Given the role of microRNAs (miRNA) in cholesterol metabolism, we hypothesized that this shift is mediated by changes in regulatory miRNAs. To assess whether a panel of pre-selected plasma miRNAs mediates the phenotype switch from cholesterol-synthesizer to cholesterol-absorber following weight loss. An untargeted serum miRNA screening approach was performed. From an existing database (N = 367), samples from participants with the highest (N = 8) and the lowest (N = 8) plasma lathosterol/campesterol ratios were selected. Three microRNAs associated with cholesterol-synthesizers and three miRNAs associated with cholesterol-absorbers were identified. Changes in these miRNAs were then evaluated in a well-controlled weight-loss study. For this, men with abdominal obesity were randomized into a no-weight-loss control group (N = 26) and a weight-loss group (N = 23) that lost 10.3 kg body weight. Pre- and post-intervention, plasma microRNA levels were measured. The screening identified miR-486-5p, miR-320b-3p and miR-185-5p as associated with the cholesterol-synthesizer phenotype, and miR-4529-3p, miR-3613-5p and miR-6776-5p with the cholesterol-absorber phenotype. One miRNA assay (miR-4529-3p) was unreliable and excluded from further analysis. Although the expected phenotype shift after weight loss was observed, changes in plasma miRNA levels were not significantly different between the two groups. In men with abdominal obesity, these five plasma miRNAs did not contribute to the observed phenotype switch from cholesterol-synthesizer towards cholesterol-absorber following weight loss.