The level and species of plasma non-esterified fatty acids are not related to elevated plasma apolipoprotein B levels in familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL), the leading cause of familial hyperlipidemia with premature coronary artery disease, has been associated with insulin resistance and elevated plasma levels of apolipoproten B (apoB) and non-esterified fatty acids (NEFA). Becaus dietary fats affect plasma cholesterol levels, and specific saturated fatty acids (FA) are particularly potent stimulators in vitro of apoB secretio from hepatocytes, we hypothesized that FCHL patients would exhibit elevations in plasma levels of total FA or specific saturated species. Five families containing 12 FCHL subjects (5 adults, 7 children and 8 normals (5 adults, 3 children) were assessed by dietary, anthropometric, and plasma measurements (glucose, insulin, lipoproteins, total NEFA, and specific FA types). After adjustment of the data for age, gender, and family affiliation, multivariate ANOVA indicated that FCHL was significantly associated with elevated plasma levels of apoB (p = 0.001) and insulin (p< 0.001) and increased body weight (p=0.043). Nevertheless, dietary intakes of total and saturated fat were comparable in the two groups, as were plasma levels of total NEFA and the major saturated species. In a study population possessing the salient features of FCHL, circulating total NEFA were not elevated, nor were specific saturated NEFA that had been associated with apoB oversecretion in vitro. Despite the speculated link between plasma FA and apoB overproduction in FCHL, our data suggest that other metabolic factors underlie this disease.

Alcohol consumption raises HDL cholesterol levels by increasing the transport rate of apolipoproteins A-I and A-II.

BACKGROUND: Moderate alcohol intake is associated with lower atherosclerosis risk, presumably due to increased HDL cholesterol (HDL-C) concentrations; however, the metabolic mechanisms of this increase are poorly understood. METHODS AND RESULTS: We tested the hypothesis that ethanol increases HDL-C by raising transport rates (TRs) of the major HDL apolipoproteins apoA-I and -II. We measured the turnover of these apolipoproteins in vivo in paired studies with and without alcohol consumption in 14 subjects. The fractional catabolic rate (FCR) and TR of radiolabeled apoA-I and -II were determined in the last 2 weeks of a 4-week Western-type metabolic diet, without (control) or with alcohol in isocaloric exchange for carbohydrates. Alcohol was given as vodka in fixed amounts ranging from 0.20 to 0.81 g. kg(-1). d(-1) (mean+/-SD 0.45+/-0.19) to reflect the usual daily intake of each subject. HDL-C concentrations increased 18% with alcohol compared with the control (Wilcoxon matched-pairs test, P=0.002). The apoA-I concentrations increased by 10% (P=0.048) and apoA-II concentrations increased by 17% (P=0.005) due to higher apoA-I and -II TRs, respectively, whereas the FCR of both apoA-I and -II did not change. The amount of alcohol consumed correlated with the degree of increase in HDL-C (Pearson's r=0.66, P=0.01) and apoA-I TR (r=0.57, P=0.03). The increase in HDL-C also correlated with the increase in apoA-I TR (r=0.61, P=0.02). CONCLUSIONS: Alcohol intake increases HDL-C in a dose-dependent fashion, associated with and possibly caused by an increase in the TR of HDL apolipoproteins apoA-I and -II.