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Rate of Production of Plasma and Very-Low-Density Lipoprotein (VLDL) Apolipoprotein C-III Is Strongly Related to the Concentration and Level of Production of VLDL Triglyceride in Male Subjects with Different Body Weights and Levels of Insulin Sensitivity

Clinical Research Institute of Montreal (J.S.C., J.D.), Quebec, Canada, H2W 1R7; the Washington University School of Medicine (B.W.P.), St. Louis, Missouri 63110; and the Toronto General Hospital (K.D.U., G.S.), Ontario, Canada M5G 2C4

Address all correspondence and requests for reprints to: Jeffrey S. Cohn, Ph.D., Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montréal, 110 Pine Avenue West, Québec, Canada, H2W 1R7. E-mail: cohnj{at}ircm.qc.ca.

Overweight individuals with reduced insulin sensitivity often have mild to moderate hypertriglyceridemia. To investigate the role of apolipoprotein (apo)C-III metabolism in the etiology of hypertriglyceridemia in these individuals, we investigated 10 male subjects with different body weights (body mass index, 24–34 kg/m²) and insulin sensitivity (homeostasis model assessment, 4.7–35.0). Total plasma and very-low-density lipoprotein (VLDL) apoC-III kinetics, as well as VLDL triglyceride (TG) and VLDL apoB kinetics, were measured with iv injected stable isotopes. The apoC-III, TG, and apoB levels in VLDL ranged from 2.9–18.2 mg/dl, 0.49–2.89 mmol/liter, and 6.7–29.3 mg/dl, respectively. Mean production rates (PRs) were: VLDL apoC-III, 20.2 ± 4.1 µmol/d (range, 8.0–44.8); VLDL TG, 26.9 ± 4.6 mmol/d (range, 10.2–51.1); and VLDL apoB, 4.4 ± 0.8 µmol/d (range, 1.5–9.1). VLDL apoC-III PRs were significantly correlated with body mass index, homeostasis model assessment, and plasma TG (r = 0.66, P < 0.05; r = 0.80, P < 0.01; r = 0.95, P < 0.001, respectively). Similar correlations were found for plasma apoC-III PRs (r = 0.70, P < 0.05; r = 0.67, P < 0.05; r = 0.80, P < 0.01, respectively). Fractional catabolic rates (FCRs) were not significantly related to metabolic variables. VLDL TG levels were strongly related to VLDL apoC-III levels (r = 0.99, P < 0.001) and VLDL apoC-III PRs (r = 0.94, P < 0.001). VLDL apoC-III levels were more strongly correlated with VLDL TG PRs (r = 0.81, P < 0.01) than with VLDL TG FCRs or VLDL apoB FCRs (r = –0.53, P = 0.12; r = –0.37, P = 0.29). These results suggest that increased hepatic production of VLDL apoC-III is characteristic of subjects with higher body weights and lower levels of insulin sensitivity and is strongly related to the plasma concentration and level of production of VLDL TG.

This work was supported by a grant from the Canadian Heart and Stroke Foundation awarded to G.S. The salary of J.S.C. was funded by a Canadian Institutes of Health Research (CIHR)/Pfizer Rx&D Investigator Award (DSC-64146), and work in his laboratory was funded by a CIHR operating grant (MOP-14684).

Abbreviations: apo, Apolipoprotein(s); BMI, body mass index; FCR, fractional catabolic rate; GC-MS, gas chromatography-mass spectrometry; HDL, high-density lipoprotein; HOMA, homeostasis model assessment; HTG, hypertriglyceridemia; IEF, isoelectric focusing; PR, production rate; TG, triglyceride; TRL, triglyceride-rich lipoprotein; VLDL, very-low-density lipoprotein.

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