Key Findings
Recent studies have reported that microRNA (MiR) plays an important role in regulating cholesterol and lipid metabolism via the following mechanisms: 1) miR-33a/b regulates ATP binding cassette transporter (ABCA1) transporter-targeted gene; 2) miR-106 regulates ABCA1 expression; 3) miR-30c reduces lipid synthesis; and 4) miR-181a increases gene expression involved in β-oxidation and decreases gene expression involved in lipid synthesis. The Canola Oil Multicentre Intervention Trial (COMIT I) was a randomized, crossover, controlled-feeding trial designed to examine the effects of 5 diets low in SFAs with varying unsaturated fatty acid profiles on endothelial function in a population with or at risk for MetS. The present study was conducted as part of the COMIT I study to investigate the effects of these 5 diets on the following: 1) the serum-mediated cholesterol efflux capacity; 2) the association between serum-mediated cholesterol efflux capacity and central obesity; and 3) the plausible molecular mechanisms of how dietary fatty acids may affect membrane fluidity measured by plasma lipophilic index (LI) and the effect of varying fatty acids on MiR expression that regulate cholesterol efflux capacity in participants from the COMIT I study. In this randomized, crossover, 5 diet-period, controlled-feeding trial, an inverse association between central obesity and serum-mediated cholesterol was found. Consumption of diets low in SFAs and high in unsaturated fatty acids increase serum-mediated cholesterol efflux capacity in participants with or at risk for MetS. The similar increase in serum-mediated cholesterol efflux in response to all diets suggests that HDL function is independent of HDL cholesterol concentrations. In summary, consumption of diets low in SFAs and high in MUFAs or PUFAs (n–6 fatty acids or n–3 fatty acids—both plant and marine derived) increased serum-mediated cholesterol efflux in participants with or at risk for MetS. The present study underscores the adverse effects of obesity on cholesterol efflux. Overweight and obese individuals will benefit from a heart-healthy diet low in SFAs and high in unsaturated fatty acids that increases cholesterol efflux, and with weight loss, cholesterol efflux would be expected to improve further.
ABSTRACT
Background: Cholesterol efflux plays an important role in preventing atherosclerosis progression. Vegetable oils with varying unsaturated fatty acid profiles favorably affect multiple cardiovascular disease risk factors; however, their effects on cholesterol efflux remain unclear. Objective:
The objectives of this study were to examine the effects of diets low in saturated fatty acids (SFAs) with varying unsaturated fatty acid profiles on serum-mediated cholesterol efflux and its association with the plasma lipophilic index and central obesity. Methods: The present study is a randomized, crossover, controlled-feeding study. Participants [men: n = 50; women: n = 51; mean ± SE age: 49.5 ± 1.2 y; body mass index (in kg/m2): 29.4 ± 0.4] at risk for or with metabolic syndrome (MetS) were randomly assigned to 5 isocaloric diets containing the treatment oils: canola oil, high oleic acid-canola oil, DHA-enriched high oleic acid-canola oil, corn oil and safflower oil blend, and flax oil and safflower oil blend. These treatment oils were incorporated into smoothies that participants consumed 2 times/d. For a 3000-kcal diet, 60 g of treatment oil was required to provide 18% of total energy per day. Each diet period was 4 wk followed by a 2- to 4-wk washout period. We quantified cholesterol efflux capacity with a validated ex vivo high-throughput cholesterol efflux assay. Statistical analyses were performed with the use of the SAS mixed-model procedure. Results: The 5 diets increased serum-mediated cholesterol efflux capacity from THP-1 macrophages similarly by 39%, 34%, 55%, 49% and 51%, respectively, compared with baseline (P < 0.05 for all). Waist circumference and abdominal adiposity were negatively correlated with serum-mediated cholesterol efflux capacity (r = -0.25, P = 0.01, r = -0.33, P = 0.02, respectively). Conclusion: Diets low in SFAs with different monounsaturated fatty acid and polyunsaturated fatty acid profiles improved serum-mediated cholesterol efflux capacity in individuals with or at risk for MetS. This mechanism may account, in part, for the cardiovascular disease benefits of diets low in SFAs and high in unsaturated fatty acids. Importantly, central obesity is inversely associated with cholesterol efflux capacity.