DETERMINANTS OF THE KINETICS OF VERY-LOW-DENSITY LIPOPROTEIN APOLIPOPROTEIN B-100 IN NONOBESE MEN

1. Apolipoprotein B-100 (ApoB) is the principal structural and functio nal protein of the pro-atherogenic lipoproteins. Elevated plasma apoB is an independent risk factor for coronary artery disease, In the pres ent study we aimed to assess the factors that determine the kinetics o f apoB in the very low-density lipoprotein (VLDL) in healthy men. 2. W e studied 17 non-obese men who were consuming an ad libitum diet and h ad the following characteristics: mean (+/- SD) age 45.5 +/- 9.7 years , body mass index (BMI) 25.1 +/- 1.4 kg/m(2), waist:hip ratio 0.91 +/- 0.04, serum cholesterol 5.2 +/- 0.6 mmol/L, triglycerides 1.08 +/- 0. 53 mmol/L, and high-density lipoprotein-cholesterol 1.24 +/- 0.31 mmol /L. Daily dietary intake was as follows: total fat 76 +/- 26 g, carboh ydrate 238 +/- 67 g, protein 103 +/- 33 g and alcohol 20 +/- 16 g. 3. The kinetics of VLDL ApoB were studied using a primed, constant infusi on (1 mg/kg per h) of 1-[C-13]-leucine over 8 h with measurement of is otopic enrichment of ApoB using gas chromatography/mass spectrometry. The fractional turnover rate of VLDL ApoB was estimated using a monoex ponential function, The mean (+/- SD) absolute hepatic secretion rate (ASR) of ApoB was 8.5 +/- 4.6 mg/kg per day and the fractional catabol ic rate (FCR) was 7.9 +/- 5.6 pools/day. The ASR was significantly cor related with the waist:hip ratio (r = 0.60; P = 0.04), bat not with ag e, BMI, weight or nutrient intake. The FCR was significantly and inver sely correlated with plasma triglycerides (r = -0.53; P = 0.03) and al cohol intake (r = -0.48; P = 0.05). 4. In conclusion the hepatic secre tion of VLDL ApoB in non-obese, healthy men is primarily determined by the waist:hip ratio, a measure of visceral fat, This is consistent wi th the hypothesis that the rate of lipid substrate supply to the liver regulates the output of ApoB, The fractional metabolism of VLDL ApoB may, however, be inversely related to alcohol intake and appears to de termine the plasma concentration of triglycerides.