Is the decreased high-density lipoprotein cholesterol in the metabolic syndrome due to cellular lipid efflux defect?

The metabolic syndrome (MS) is associated with cardiovascular disease. The low high-density lipoprotein cholesterol (HDL-C) seen in the MS is associated with increased hepatic secretion of apolipoprotein B-containing lipoproteins. Patients with low HDL-C and abnormal cellular lipid efflux due to ABCA1 gene defects (Tangier disease) also have elevated plasma triglycerides. In the present study, we examined the cellular cholesterol and phospholipid efflux in patients with low HDL-C and features of the MS. Forty-four patients with a HDL-C below the fifth percentile for age and gender were selected. The MS was defined by a low HDL-C and at least two additional features: body mass index at least 30 kg/m(2), plasma triglycerides at least 150 mg/dl, fasting glucose at least 110 mg/dl, and blood pressure at least 130/85 mm Hg. Cellular lipid efflux was examined on fibroblasts obtained from study subjects, nine normal controls and six subjects with Tangier disease. In 22 patients identified with the MS, HDL-C was 21 +/- 7 mg/dl, triglyceride levels were 340 +/- 157 mg/dl, and cellular cholesterol and phospholipid efflux were 107 +/- 18% and 105 +/- 17% of controls, respectively. No patient with the MS and low HDL-C showed a cellular lipid efflux defect. We conclude that primary cellular lipid efflux defects do not contribute to the low HDL-C frequently encountered in the MS.