Alterations in lipid kinetics in men with HIV-dyslipidemia

Department of Internal Medicine and Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri 63110 Submitted 20 March 2003 ; accepted in final form 9 May 2003 Hypertriglyceridemia is common in individuals with human immunodeficiency (HIV) infection, but the mechanisms responsible for increased plasma triglyceride (TG) concentrations are not clear. We evaluated fatty acid and VLDL-TG kinetics during basal conditions and during a glucose infusion that resulted in typical postprandial plasma glucose and insulin concentrations in six men with HIV-dyslipidemia [body mass index (BMI): 28 ± 2 kg/m 2 ] and six healthy men (BMI: 26 ± 2 kg/m 2 ). VLDL-TG secretion and palmitate rate of appearance (R a ) in plasma were measured by using stable-isotope-labeled tracer techniques. Basal palmitate R a and VLDL-TG secretion rates were greater ( P < 0.01 for both) in men with HIV-dyslipidemia (1.04 ± 0.07 µmol palmitate · kg - 1 · min - 1 and 5.7 ± 0.6 µmol VLDL-TG · l plasma - 1 · min - 1 ) than in healthy men (0.67 ± 0.08 µmol palmitate · kg - 1 · min - 1 and 3.0 ± 0.5 µmol VLDL-TG · l plasma - 1 · min - 1 ). Basal VLDL-TG plasma clearance was lower in men with HIV-dyslipidemia (13 ± 1 ml/min) than in healthy men (19 ± 2 ml/min; P < 0.05). Glucose infusion decreased palmitate R a (by 50%) and the VLDL-TG secretion rate (by 30%) in both groups, but the VLDL-TG secretion rate remained higher ( P < 0.05) in subjects with HIV-dyslipidemia. These findings demonstrate that increased secretion of VLDL-TG and decreased plasma VLDL-TG clearance, during both fasting and fed conditions, contribute to hypertriglyceridemia in men with HIV-dyslipidemia. Although it is likely that increased free fatty acid release from adipose tissue contributes to the increase in basal VLDL-TG concentration, other factors must be involved, because insulin-induced suppression of lipolysis and systemic fatty acid availability did not normalize the VLDL-TG secretion rate. stable isotopes; lipolysis; hypertriglyceridemia; metabolism; human immunodeficiency virus Address for reprint requests and other correspondence: S. Klein, Center for Human Nutrition, Washington Univ. School of Medicine, 660 S. Euclid Ave., Campus Box 8031, St. Louis, MO 63110 (E-mail: sklein{at}im.wustl.edu ).