title: Hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 studied with a stable isotope technique in men with visceral obesity.
abstract: OBJECTIVE
  To test the hypothesis that the hepatic secretion of very-low-density lipoprotein (VLDL) apolipoprotein B-100 (apoB) is increased in men with visceral obesity and to examine whether the oversecretion of this apolipoprotein is related to insulin resistance and increased hepatic availability of lipid substrates.
  
  
  METHODS
  16 obese men (body mass index (BMI) > 30 kg/m2, waist circumference > 100 cm) and 16 non-obese, age matched men, were studied.
  
  
  METHODS
  The hepatic secretion of VLDL apoB was measured using a primed (1 mg/kg), constant (1 mg/kg/h), intravenous infusion of 1-[13C]-leucine. Isotopic enrichment of VLDL apoB was determined using gas-chromatography mass spectrometry and a multi-compartmental model (SAAM-II) was used to estimate the fractional turnover rate of VLDL apoB.
  
  
  RESULTS
  Plasma concentrations of total cholesterol, triglyceride, glucose, insulin, mevalonic acid and lathosterol, as well as dietary fat intake, were significantly higher (P < 0.05) in obese than control subjects. The obese subjects had significantly lower high-density-lipoprotein cholesterol (P < 0.01). VLDL apoB pool size and hepatic secretion rate (mg/kg fat free mass/d) were significantly higher in the obese than non-obese subjects (P < 0.02). The fractional catabolic rate of VLDL apoB was lower in the obese subjects compared with controls, but the difference did not attain conventional significance (P=0.053). In pooled analysis, there was a significant positive association (P < 0.05) between VLDL apoB secretion rate (mg/kg fat free mass/d) and waist-to-hip ratio (WHR), waist circumference, and fasting plasma triglyceride, insulin and glucose concentrations. In multiple linear regression analysis, the association between VLDL apoB secretion and fasting insulin concentration was independent of age, apolipoprotein E (apoE) genotype, mevalonic acid concentration, free fatty acid concentration and fat intake.
  
  
  CONCLUSIONS
  Our findings are consistent with the hypothesis that in visceral obesity, insulin resistance and the associated increased lipid substrate supply to the liver contribute to hepatic oversecretion of apoB; expansion in the VLDL apoB pool size may also be due to a catabolic defect related to insulin resistance.
authors.affiliation: University Department of Medicine and West Australia Heart Research Institute, University of Western Australia, Royal Perth Hospital.
authors.forename: F M
authors.initials: FM
authors.lastname: Riches
authors.forename: G F
authors.initials: GF
authors.lastname: Watts
authors.forename: R P
authors.initials: RP
authors.lastname: Naoumova
authors.forename: J M
authors.initials: JM
authors.lastname: Kelly
authors.forename: K D
authors.initials: KD
authors.lastname: Croft
authors.forename: G R
authors.initials: GR
authors.lastname: Thompson
mesh_terms: D000328:Adult; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D001824:Body Constitution; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D004041:Dietary Fats / Q000008:administration & dosage; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007328:Insulin / Q000097:blood; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000503:physiopathology*; D014280:Triglycerides / Q000097:blood
chemical_list: D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D001786:Blood Glucose; D008076:Cholesterol, HDL; D015243:Cholesterol, VLDL; D004041:Dietary Fats; D007328:Insulin; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D002784:Cholesterol