Disturbance of apolipoprotein B100 containing lipoprotein metabolism in severe hyperlipidemic and lipodystrophic HIV patients on combined antiretroviral therapy: evidences of insulin resistance effect.
The aim was to study the mechanisms involved in the dyslipidemia associated with lipodystrophy in HIV infected patients on antiretroviral therapy (ART). We investigated the in vivo kinetics of apolipoprotein B100 (apoB) containing lipoproteins using a 14 h primed constant infusion of [5,5,5, (2)H(3)] leucine and compartmental modelling in normolipidemic without lipodystrophy (7 patients, NLD) or dyslipidemic with lipodystrophy (7 patients, LD) treated with ART. Subjects in group LD showed higher plasma triglycerides (5.73+/-3.58 vs 1.29+/-0.54 g/L, p<0.005), total cholesterol (2.98+/-0.95 vs 1.74+/-0.26 g/L, p<0.05), apoB (1.49+/-1.11 vs 0.51+/-0.11 g/L, p<0.005) and apolipoprotein CIII in apoB containing lipoproteins (117.7+/-42.2 vs 22.6+/-23.9 g/L, p<0.005). LD subjects exhibited an insulin resistant as observed by higher HOMA (3.44+/-1.62 vs 1.60+/-0.61, p<0.05). They exhibited an increase in VLDL (1.24+/-0.33 vs 0.80+/-0.21 mg/kg/h, p<0.05), decrease in IDL (0.20+/-0.10 vs 0.48+/-0.24 mg/kg/h, p<0.05) and no difference in LDL (0.38+/-0.19 vs 0.45+/-0.25 mg/kg/h) production rate. LD subject also showed a dramatic decrease in transformation of VLDL to IDL (0.013+/-0.010 vs 0.258+/-0.206 h(-1), p<0.005) and IDL to LDL (0.088+/-0.093 vs 0.366+/-0.189 h(-1), p<0.05) and a decrease in fractional catabolic rate (FCR) of VLDL (0.199+/-0.132 vs 0.555+/-0.398 h(-1), p<0.05), IDL (0.110+/-0.08 vs 0.523+/-0.275 h(-1), p<0.05) and LDL (0.010+/-0.005 vs 0.025+/-0.014 h(-1), p<0.05). These disturbances, overproduction and an overall delayed catabolism of apoB, are similar to those observed using the same protocol in insulin resistant subjects. Our study suggests that metabolic disturbance of apoB100 observed in lipodystrophic HIV in combined antiretroviral therapy are consecutive to insulin resistance induced by the treatment.
Ouguerram
Khadija
K
Centre de Recherche en Nutrition Humaine, INSERM U 915, Hotel Dieu, 44035 Nantes cedex 1, France. Khadija.Ouguerram@sante.univ-nantes.fr
Zair
Yassine
Y
Billon
Stéphanie
S
Chétiveaux
Maud
M
Brunet-François
Cécile
C
Ngohou-Bach
Kalyane
K
Allavena
Clotilde
C
Reliquet
Veronique
V
Milpied
Brigitte
B
Magot
Thierry
T
Raffi
François
F
Krempf
Michel
M
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D053299:Apolipoprotein B-100 / Q000378:metabolism*; D053305:Apolipoprotein C-III / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000378:metabolism*; D006801:Humans; D006949:Hyperlipidemias / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D007700:Kinetics; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular
D053299:Apolipoprotein B-100; D053305:Apolipoprotein C-III; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D008074:Lipoproteins