title: Stable isotopes show a direct relation between VLDL apoB overproduction and serum triglyceride levels and indicate a metabolically and biochemically coherent basis for familial combined hyperlipidemia.
abstract: Familial combined hyperlipidemia (FCHL) may be genetically and metabolically more heterogeneous than previously thought. A consistent feature is an increase in circulating very-low-density lipoprotein (VLDL) apolipoprotein (apo) B, which could be due to either an increase in apoB production or a decrease in its catabolism. Therefore, we directly measured VLDL apoB production in the postabsorptive state in seven FCHL subjects (four male, three female) and seven normal control subjects (three male, four female) by using L-[1-13C]leucine as an endogenous label. Mean age and body mass index did not differ significantly between the two groups. The mean total cholesterol levels were 4.7 +/- 0.8 and 8.8 +/- 1.6 mmol/L (+/- SD, P < .01) and the mean triglyceride levels were 0.84 +/- 0.14 and 3.30 +/- 1.10 mmol/L (+/- SD, P < .01) in the control and FCHL groups, respectively. Although the fractional production rate of VLDL apoB was 38% lower in the FCHL group than in the control subjects (0.11 +/- 0.03 versus 0.18 +/- 0.02 pool/h; mean +/- SD, P < .01), its absolute production rate was 2.7 times greater (534 +/- 193 micrograms/kg per hour in FCHL versus 196 +/- 71 micrograms/kg per hour in control subjects; mean +/- SD, P < .01). There was a linear relation (r = 0.8, P = .03) between triglyceride levels and the VLDL apoB production rate in FCHL, the slope of which indicated a similar VLDL triglyceride-to-apoB ratio in the FCHL and control groups. We conclude that FCHL is a metabolically coherent disorder and that the increase in circulating apoB and triglyceride levels in FCHL is due to secretion of an increased number of VLDL particles, each containing, on average, a normal amount of triglyceride and one molecule of apoB.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Molecular Medicine, MRC Clinical Research Centre, Harrow, England.
authors.forename: S
authors.initials: S
authors.lastname: Venkatesan
authors.forename: P
authors.initials: P
authors.lastname: Cullen
authors.forename: P
authors.initials: P
authors.lastname: Pacy
authors.forename: D
authors.initials: D
authors.lastname: Halliday
authors.forename: J
authors.initials: J
authors.lastname: Scott
mesh_terms: D000328:Adult; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000378:metabolism*; D002247:Carbon Isotopes; D004591:Electrophoresis, Polyacrylamide Gel; D005192:Family Health; D005260:Female; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D007700:Kinetics; D007930:Leucine; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D014280:Triglycerides / Q000097:blood*
chemical_list: D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D002247:Carbon Isotopes; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D007930:Leucine