Alterations in lipid kinetics in men with HIV-dyslipidemia.
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/m2] and six healthy men (BMI: 26 +/- 2 kg/m2). VLDL-TG secretion and palmitate rate of appearance (Ra) in plasma were measured by using stable-isotope-labeled tracer techniques. Basal palmitate Ra and VLDL-TG secretion rates were greater (P < 0.01 for both) in men with HIV-dyslipidemia (1.04 +/- 0.07 micromol palmitate x kg-1 x min-1 and 5.7 +/- 0.6 micromol VLDL-TG x l plasma-1 x min-1) than in healthy men (0.67 +/- 0.08 micromol palmitate. kg-1 x min-1 and 3.0 +/- 0.5 micromol VLDL-TG x l plasma-1 x 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 Ra (by approximately 50%) and the VLDL-TG secretion rate (by approximately 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.
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
D N
DN
Reeds
B
B
Mittendorfer
B W
BW
Patterson
W G
WG
Powderly
K E
KE
Yarasheski
S
S
Klein
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001786:Blood Glucose; D015243:Cholesterol, VLDL / Q000493:pharmacokinetics*; D005947:Glucose / Q000008:administration & dosage; D039682:HIV-Associated Lipodystrophy Syndrome / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D006946:Hyperinsulinism / Q000378:metabolism; D015228:Hypertriglyceridemia / Q000378:metabolism / Q000821:virology*; D007328:Insulin / Q000097:blood; D007554:Isotopes; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010168:Palmitates / Q000493:pharmacokinetics; D014280:Triglycerides / Q000493:pharmacokinetics*
D001786:Blood Glucose; D015243:Cholesterol, VLDL; D007328:Insulin; D007554:Isotopes; D010168:Palmitates; D014280:Triglycerides; D005947:Glucose