Modest Diet-Induced Weight-Loss Reduces Macrophage Cholesterol Efflux to Plasma of Metabolic Syndrome Patients

BACKGROUND— Obesity-linked metabolic syndrome (MetS) is associated with a dyslipidemic profile that includes hypertriglyceridemia and low plasma high-density lipoprotein cholesterol (HDL-C). HDL initiates reverse cholesterol transport (RCT) via macrophage cholesterol efflux (MCE). Some hypothesize that dyslipidemic patients have impaired RCT. MCE to patient plasma, a metric of HDL function, inversely correlates with atherosclerotic burden. Paradoxically, MCE to plasma of hypertriglyceridemic subjects is higher than that to normolipidemic (NL) plasma. OBJECTIVE— Although weight-loss reduces dyslipidemia, its effect on MCE to the plasma of obese, MetS patients is unknown. Thus, we tested the hypothesis that reducing dyslipidemia with weight-loss reduces the MCE capacity of MetS plasma to that of NL plasma. METHODS— Cholesterol efflux (MCE) from THP-1 macrophages to plasma from NL controls and to obese, MetS patients before and after weight-loss was measured. RESULTS— MCE to plasma of obese, MetS patients was higher than that to control plasma (p=0.006). Weight-loss in MetS patients (mean = −9.77 kg) reduced dyslipidemia, insulin resistance and systolic blood pressure. HDL-C was unchanged and apolipoprotein A-I decreased with weight-loss. Weight-loss in MetS patients normalized MCE (p<0.001) CONCLUSIONS— While the initial acceptor of macrophage cholesterol efflux is HDL, the elevated apo B lipoproteins are a cholesterol sink that increase MCE in MetS patients. Weight loss results in decreased apo B-lipoproteins and decreased MCE to plasma of MetS patients. Management included a prescreening of physical and laboratory data initial pre entry visit. Fasting glucose and lipid profile (total cholesterol, triglyceride, HDL-C and calculated LDL-C), liver function tests, blood urea nitrogen (BUN), creatinine, and serum insulin were measured. Insulin resistance was estimated on the basis of fasting glucose and serum insulin levels and the homeostatic model assessment of insulin resistance (HOMA-IR). The MCE assays, described in detail below, were performed on all samples. Both anthropometric and laboratory data were collected at the baseline visit, prior to entering the weight management program, and 4–6 weeks after entry. Exclusion criteria for patients and controls included the presence of a known eating disorder, active cancer diagnosis, use of lithium or steroids, type 1 diabetes mellitus, active inflammatory bowel disease, active gout, liver disease, cardiovascular event the preceding months, an endocrine cause for obesity, pregnancy treatment diuretic.