Effect of weight loss on HDL-apoA-II kinetics in the metabolic syndrome

Reduced HDL (high-density lipoprotein) concentration in the MetS (metabolic syndrome) is associated with increased risk of cardiovascular disease and is related to defects in HDL-apoA-II (apolipoprotein A-II) kinetics. Dietary restriction is the most commonly used weight loss strategy. In the present study, we examined the effect of weight loss on HDL-apoA-II kinetics in men with the MetS at the start and end of a 16-week intervention trial of a hypocaloric low-fat diet (n=20) compared with a weight maintenance diet (n=15), using a stable isotope technique and compartmental modelling. The low-fat diet achieved a significant reduction (P<0.01) in BMI (body mass index), abdominal fat compartments and HOMA (homoeostasis model assessment) score compared with weight maintenance. Weight loss also significantly (P<0.05) decreased both the production rate (-23%) and FCR (fractional catabolic rate) (-12%) of HDL-apoA-II, accounting for a net decrease in apoA-II concentration (-9%). Reductions in the HDL-apoA-II production rate were significantly associated with changes in body weight (r=0.683, P<0.01), plasma triacylglycerols (triglycerides) (r=0.607, P<0.01) and, to a lesser extent, plasma insulin (r=0.440, P=0.059) and HOMA-IR (HOMA of insulin resistance) (r=0.425, P=0.069). Changes in the apoA-II FCR were also significantly associated with reductions in visceral adipose tissue mass (r=0.561, P=0.010). In conclusion, in obese men with the MetS, short-term weight loss with a low-fat low-caloric diet lowers plasma apoA-II concentrations by decreasing both the production and catabolism of HDL-apoA-II. The cardiometabolic significance of this effect on HDL metabolism remains to be investigated further.