A fat load raises CETP mass and cholesteryl ester transfer while lowering HDL cholesterol in obese metabolic syndrome men, unaffected by statin or statin-ezetimibe treatment (Clin Endocrinol 2008)

Original title: Lipid-lowering therapy does not affect the postprandial drop in high density lipoprotein-cholesterol (HDL-c) plasma levels in obese men with metabolic syndrome: a randomized double blind crossover trial

Clin Endocrinol (Oxf) · 3 April 2008 · 6

Hajer GR, Dallinga-Thie GM, van Vark-van der Zee LC, Olijhoek JK, Visseren FL

In a randomized, double-blind, crossover trial, 15 nonsmoking, obese men with metabolic syndrome received simvastatin 80 mg or simvastatin/ezetimibe 10 mg/10 mg for 6 weeks each, with postprandial HDL cholesterol metabolism assessed via oral fat loading. Fasting HDL cholesterol remained stable and was similar across no treatment, simvastatin, and simvastatin/ezetimibe (1.15 +/- 0.04, 1.16 +/- 0.05, and 1.11 +/- 0.04 mmol/l). Fat loading induced an 11% drop in HDL cholesterol (to 1.02 +/- 0.05 mmol/l, P < 0.001), unaffected by either treatment, while total cholesteryl ester transfer increased from 9.73 +/- 0.70 to 12.20 +/- 0.67 nmol/ml/h (P = 0.004). Four hours after fat loading, cholesteryl ester transfer protein (CETP) mass was increased and adiponectin decreased, irrespective of treatment, pointing to a role for intra-abdominal fat in the postprandial HDL cholesterol decline.

Original abstract

Introduction: The postprandial lipid metabolism in metabolic syndrome patients is disturbed and may add to the increased cardiovascular risk in these patients. It is not known whether postprandial high density lipoprotein-cholesterol (HDL-c) metabolism is also affected and whether this can be influenced by statin and/or ezetimibe treatment.

Methods: Prospective, randomized, double blind, crossover trial comparing simvastatin 80 mg with simvastatin/ezetimibe 10 mg/10 mg treatment for 6 weeks on postprandial HDL-c metabolism in 15, nonsmoking, male, obese metabolic syndrome patients (Adult Treatment Panel III, ATPIII). Only study medication was allowed. HDL-c concentrations, cholesteryl ester transfer (CET), CET protein (CETP) mass and adiponectin were measured before and after oral fat loading. ClinicalTrials.gov NCT00189085.

Results: Plasma HDL-c levels remained stable during continuous fasting following an overnight fast. Pre-fat load HDL-c concentrations without treatment, after simvastatin and simvastatin/ezetimibe treatment were 1.15 +/- 0.04, 1.16 +/- 0.05 and 1.11 +/- 0.04 mmol/l. Fat load induced a 11% drop in HDL-c plasma levels; 1.02 +/- 0.05 mmol/l (P < 0.001) which was not affected by either therapy. Triglyceride levels during fat load were similar after both treatments. Total CET increased from 9.73 +/- 0.70 to 12.20 +/- 0.67 nmol/ml/h (P = 0.004). Four hours after fat loading CETP mass was increased while adiponectin levels were decreased, irrespective of treatment.

Discussion: HDL-c levels decrease as CET increases after fat loading in obese metabolic syndrome patients. This is not influenced by either simvastatin or simvastatin/ezetimibe treatment. After fat loading, CETP mass and CET increased, and adiponectin decreased pointing towards a potential role for intra-abdominal fat. Decreased postprandial HDL-c levels may contribute to the increased cardiovascular risk in metabolic syndrome patients on top of already low HDL-c levels.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.