ABNORMALITIES OF VERY-LOW-DENSITY LIPOPROTEIN APOLIPOPROTEIN B-100 METABOLISM CONTRIBUTE TO THE DYSLIPIDEMIA OF ADULT GROWTH-HORMONE DEFICIENCY

Increased cardiovascular mortality in adult growth hormone deficiency (GHD) may be, in part, explained by the dyslipidaemia associated with this condition It is possible that abnormalities of very low density l ipoprotein apolipoprotein B-100 (VLDL apoB) metabolism contribute to t his dyslipidaemia. To test this hypothesis, we measured VLDL apoB kine tics in adult GH deficient patients (4 females, 3 males; age 50.1 +/- 4.7 yr (mean +/- SEM); BMI 28.2 +/- 1.1 kg/m(2); total cholesterol (TC ) 6.6 +/- 0.3 mmol/l; triglyceride (TG) 2.8 +/- 0.6 mmol/l; HDL choles terol 1.1 +/- 0.1 mmol/l) and in control subjects (4 females, 3 male; age 47.0 +/- 4.7 yr; BMI 27.0 +/- 2.6 kg/m(2); TC 5.0 +/- 0.4 mmol/l; TG 0.9 +/- 0.2 mmol/l; HDL cholesterol 1.4 +/- 0.1 mmol/l). [1-C-13] l eucine was administered by a primed (1mg/kg), constant intravenous inf usion (1mg/kg/hr) and VLDL apoB enrichment with C-13 leucine was deter mined using gas-chromatography mass-spectrometry. The GHD patients had a significantly higher hepatic secretion rate of VLDL apoB (15.5 +/- 1.8 mg/kg/day vs 9.4 +/- 0.6 mg/kg/day p = 0.007) and reduced cataboli sm of VLDL apoB (metabolic clearance rate; 12.3 +/- 1.7 ml/min vs 24.3 +/- 4.8 ml/min p < 0.05) compared with control subjects. These findin gs suggest that GH is integrally involved in tile regulation of VLDL a poB metabolism.