Boris Hansel1, Dominique Bonnefont-Rousselot2, Alexina Orsoni3, Randa Bittar4, Philippe Giral5, Ronan Roussel6, Michel Marre6, Kamel Mohammedi7, Eric Bruckert5, Martin John Chapman3, Anatol Kontush3. 1. Département d'Endocrinologie, Diabétologie et Nutrition, DHU FIRE, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, France; INSERM U1138, Centre de Recherche des Cordeliers, Paris, France; Université Paris-Diderot, Paris 7, Paris, France. Electronic address: boris.hansel@aphp.fr. 2. Service de Biochimie Métabolique, Groupe hospitalier Pitié-Salpêtrière-Charles Foix, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; INSERM UMRS 1166 ICAN, Université Pierre et Marie Curie Paris 6, Hôpital de la Pitie, Paris, France; Faculté de Pharmacie, Université Paris Descartes, Paris, France. 3. INSERM UMRS 1166 ICAN, Université Pierre et Marie Curie Paris 6, Hôpital de la Pitie, Paris, France. 4. Service de Biochimie Métabolique, Groupe hospitalier Pitié-Salpêtrière-Charles Foix, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; INSERM UMRS 1166 ICAN, Université Pierre et Marie Curie Paris 6, Hôpital de la Pitie, Paris, France. 5. Service d'Endocrinologie-Métabolisme, AP-HP, Hôpital de la Pitié, Paris, France. 6. Département d'Endocrinologie, Diabétologie et Nutrition, DHU FIRE, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, France; INSERM U1138, Centre de Recherche des Cordeliers, Paris, France; Université Paris-Diderot, Paris 7, Paris, France. 7. Département d'Endocrinologie, Diabétologie et Nutrition, DHU FIRE, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, France; INSERM U1138, Centre de Recherche des Cordeliers, Paris, France.
Abstract
BACKGROUND: Metabolic syndrome (MetS) is associated with altered lipoprotein metabolism and impairment in the functionality of small, dense high-density lipoprotein (HDL) particles secondary to compositional alterations. OBJECTIVE: The objective of this study was to investigate the capacity of a lifestyle program to improve the composition and antioxidative function (AOX) of small dense HDL3c in MetS. METHODS: Patients with MetS (n = 33) not taking lipid-lowering drugs were recruited to follow a 12-week educational program to reduce caloric intake and to increase physical activity. HDL subfractions were preparatively isolated by isopycnic density-gradient ultracentrifugation. AOX of HDL3c was assessed as its capacity to inhibit low-density lipoprotein oxidation induced by an azoinitiator. RESULTS: AOX of HDL3c was significantly improved (mean reduction in the propagation rate of low-density lipoprotein oxidation by HDL3c, -6.8%, P = .03) and systemic oxidative stress, assessed as plasma levels of 8-isoprostanes, tended to decrease in normocholesterolemic MetS patients (low-density lipoprotein cholesterol [LDL-C] < 130 mg/dL) but not in patients with elevated LDL-C levels and in the whole study population. In both the whole study population and the normocholesterolemic subgroup, lifestyle intervention resulted in a significant degree of normalization of HDL3c composition, (enrichment in apolipoprotein A-I and cholesteryl esters, depletion in triglycerides), which was more pronounced at LDL-C < 130 mg/dL. CONCLUSION: In patients with MetS, a lifestyle program improves AOX of small, dense HDL in subjects with normal LDL-C levels. Correction of HDL composition, involving partial normalization of apoA-I content and core lipid composition, 2 central features of the lipid hydroperoxide-inactivating capacity of HDL, may account for this effect.
BACKGROUND:Metabolic syndrome (MetS) is associated with altered lipoprotein metabolism and impairment in the functionality of small, dense high-density lipoprotein (HDL) particles secondary to compositional alterations. OBJECTIVE: The objective of this study was to investigate the capacity of a lifestyle program to improve the composition and antioxidative function (AOX) of small dense HDL3c in MetS. METHODS:Patients with MetS (n = 33) not taking lipid-lowering drugs were recruited to follow a 12-week educational program to reduce caloric intake and to increase physical activity. HDL subfractions were preparatively isolated by isopycnic density-gradient ultracentrifugation. AOX of HDL3c was assessed as its capacity to inhibit low-density lipoprotein oxidation induced by an azoinitiator. RESULTS: AOX of HDL3c was significantly improved (mean reduction in the propagation rate of low-density lipoprotein oxidation by HDL3c, -6.8%, P = .03) and systemic oxidative stress, assessed as plasma levels of 8-isoprostanes, tended to decrease in normocholesterolemic MetS patients (low-density lipoprotein cholesterol [LDL-C] < 130 mg/dL) but not in patients with elevated LDL-C levels and in the whole study population. In both the whole study population and the normocholesterolemic subgroup, lifestyle intervention resulted in a significant degree of normalization of HDL3c composition, (enrichment in apolipoprotein A-I and cholesteryl esters, depletion in triglycerides), which was more pronounced at LDL-C < 130 mg/dL. CONCLUSION: In patients with MetS, a lifestyle program improves AOX of small, dense HDL in subjects with normal LDL-C levels. Correction of HDL composition, involving partial normalization of apoA-I content and core lipid composition, 2 central features of the lipid hydroperoxide-inactivating capacity of HDL, may account for this effect.