Modest diet-induced weight loss reduces macrophage cholesterol efflux to plasma of patients with metabolic syndrome

Background: Obesity-linked metabolic syndrome (MetS) is associated with a dyslipidemic profile that includes hypertriglyceridemia and low plasma high-density lipoprotein (HDL) cholesterol. HDL initiates reverse cholesterol transport via macrophage cholesterol efflux (MCE). Some hypothesize that dyslipidemic patients have impaired reverse cholesterol transport. 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 patients with MetS 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 patients with MetS before and after weight loss was measured.

Results: MCE to plasma of obese patients with MetS was higher than that of control plasma (P = .006). Weight loss in patients with MetS (mean, -9.77 kg) reduced dyslipidemia, insulin resistance, and systolic blood pressure. HDL cholesterol was unchanged, and apolipoprotein A-I decreased with weight loss. Weight loss in patients with MetS normalized MCE (P < .001) to that of NL subjects. MCE correlated with apolipoprotein B levels (r² = 0.13-0.38). Chromatography showed that macrophage cholesterol initially associates with HDL but accumulates in apolipoprotein B-containing lipoproteins at later times.

Conclusions: Although the initial acceptor of MCE is HDL, the elevated apolipoprotein B lipoproteins are a cholesterol sink that increases MCE in patients with MetS. Weight loss results in decreased apolipoprotein B lipoproteins and decreased MCE to plasma of patients with MetS.