title: Disturbance of apolipoprotein B100 containing lipoprotein metabolism in severe hyperlipidemic and lipodystrophic HIV patients on combined antiretroviral therapy: evidences of insulin resistance effect.
abstract: 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.
authors.affiliation: Centre de Recherche en Nutrition Humaine, INSERM U 915, Hotel Dieu, 44035 Nantes cedex 1, France. Khadija.Ouguerram@sante.univ-nantes.fr
authors.forename: Khadija
authors.initials: K
authors.lastname: Ouguerram
authors.forename: Yassine
authors.initials: Y
authors.lastname: Zair
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Billon
authors.forename: Maud
authors.initials: M
authors.lastname: Chétiveaux
authors.forename: Cécile
authors.initials: C
authors.lastname: Brunet-François
authors.forename: Kalyane
authors.initials: K
authors.lastname: Ngohou-Bach
authors.forename: Clotilde
authors.initials: C
authors.lastname: Allavena
authors.forename: Veronique
authors.initials: V
authors.lastname: Reliquet
authors.forename: Brigitte
authors.initials: B
authors.lastname: Milpied
authors.forename: Thierry
authors.initials: T
authors.lastname: Magot
authors.forename: François
authors.initials: F
authors.lastname: Raffi
authors.forename: Michel
authors.initials: M
authors.lastname: Krempf
mesh_terms: 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
chemical_list: D053299:Apolipoprotein B-100; D053305:Apolipoprotein C-III; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D008074:Lipoproteins