Determinants of the Kinetics of Very Low‐density Lipoprotein Apolipoprotein B‐100 in Non‐obese Men

Abstract

1. Apolipoprotein B-100 (ApoB) is the principal structural and functional protein of the pro-atherogenic lipoproteins. Elevated plasma apoB is an independent risk factor for coronary artery disease. In the present study we aimed to assess the factors that determine the kinetics of apoB in the very low-density lipoprotein (VLDL) in healthy men. 2. We studied 17 non-obese men who were consuming an ad libitum diet and had the following characteristics: mean (+/-SD) age 45.5 +/- 9.7 years, body mass index (BMI) 25.1 +/- 1.4 kg/m2, 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, carbohydrate 238 +/- 67 g, protein 103 +/- 33 g and alcohol 20 +/- 16 g. 3. The kinetics of VLDL ApoB were studied using a primed, constant infusion (1 mg/kg per h) of 1-[13C]-leucine over 8 h with measurement of isotopic enrichment of ApoB using gas chromatography/mass spectrometry. The fractional turnover rate of VLDL ApoB was estimated using a monoexponential function. The mean (+/-SD) absolute hepatic secretion rate (ASR) of ApoB was 8.5 +/- 4.6 mg/kg per day and the fractional catabolic rate (FCR) was 7.9 +/- 5.6 pools/day. The ASR was significantly correlated with the waist:hip ratio (r = 0.60; P = 0.04), but not with age, BMI, weight or nutrient intake. The FCR was significantly and inversely correlated with plasma triglycerides (r = -0.53; P = 0.03) and alcohol intake (r = -0.48; P = 0.05). 4. In conclusion, the hepatic secretion of VLDL ApoB in nonobese, healthy men is primarily determined by the waist:hip ratio, a measure of visceral fat. This is consistent with the hypothesis that the rate of lipid substrate supply in the liver regulates the output of ApoB. The fractional catabolism of VLDL ApoB may, however, be inversely related to alcohol intake and appears to determine the plasma concentration of triglycerides.

Fat Compartments and Apolipoprotein B‐100 Kinetics in Overweight‐Obese Men

“…Seven of the subjects had impaired fasting glucose (i.e., plasma glucose concentrations between 6.1 and 6.9 mM) and two had diabetes mellitus (i.e., fasting glucose concentrations ≥7.0 mM) (29). VLDL‐apoB secretion and fractional catabolism of our obese subjects were also significantly ( p < 0.05) higher and lower (both by 60%), respectively, than this control population (15, 16).…”

“…We have also reported elsewhere that hepatic VLDL‐apoB secretion is directly and strongly correlated with visceral adipose tissue mass, measured as visceral adipose tissue area at L4, before and after weight reduction in obese subjects (16, 18). We have also shown that the waist‐to‐hip ratio independently predicts VLDL‐apoB secretion in men with a wide range of adiposity (15). The present observation is consistent with and extends our previous reports.…”

“…VLDL‐apoB kinetics were measured after a primed (1 mg/kg), constant (1 mg/kg per hour) intravenous infusion (10 hour) of 1‐[ 13 C]‐leucine (99.5% enrichment) (Tracer Technologies, Somerville, MA), as previously described in detail (13, 15, 23). VLDL‐apoB was isolated by preparative ultracentrifugation, precipitated by isopropanol, and quantified by Lowry method (28).…”

Association between skeletal muscle fat content and very‐low‐density lipoprotein‐apolipoprotein B‐100 transport in obesity: effect of weight loss

“…Using data from the same study cohort , we have previously reported that, compared with 15 (9 men and 6 women) non‐obese age‐matched subjects, our obese subjects had a significantly (p < 0.05 for all) higher VLDL‐apoB‐100 concentration (137 ± 52 vs. 51 ± 20 mg/l) and secretion rate (18.6 ± 5.0 vs. 15.6 ± 4.4 mg/kg/day) and a reduced FCR (4.2 ± 2.4 vs. 7.5 ± 2.9 pools/day). Furthermore, the 25 obese subjects had significantly higher visceral (265 ± 104 vs. 83.8 ± 23.3 cm 2 ) and subcutaneous fat at L3 (310 ± 128 vs. 141 ± 43.3 cm 2 ) compared with non‐obese subjects .…”

“…Average daily energy and nutrient intake was 8339 ± 2190 kJ, 37 ± 6% energy from fat, 39 ± 5% energy from carbohydrates, 21 ± 4% energy from protein and 3 ± 3% energy from alcohol. Using data from the same study cohort [4], we have previously reported that, compared with 15 (9 men and 6 women) non-obese age-matched subjects, our obese subjects had a significantly (p < 0.05 for all) higher VLDL-apoB-100 concentration (137 ± 52 vs. 51 ± 20 mg/l) and secretion rate ( [11]. When the subjects were classified into two groups according to insulin sensitivity status (using a HOMA score of 2.6 as the cut-off [10]), the IR group had significantly higher plasma glucose and insulin concentrations and HOMA score than the IS group.…”