Lifestyle intervention enhances high-density lipoprotein function among patients with metabolic syndrome only at normal low-density lipoprotein cholesterol plasma levels.
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.



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.



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.



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.



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.
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.
Boris
B
Hansel
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.
Dominique
D
Bonnefont-Rousselot
INSERM UMRS 1166 ICAN, Université Pierre et Marie Curie Paris 6, Hôpital de la Pitie, Paris, France.
Alexina
A
Orsoni
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.
Randa
R
Bittar
Service d'Endocrinologie-Métabolisme, AP-HP, Hôpital de la Pitié, Paris, France.
Philippe
P
Giral
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.
Ronan
R
Roussel
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.
Michel
M
Marre
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.
Kamel
K
Mohammedi
Service d'Endocrinologie-Métabolisme, AP-HP, Hôpital de la Pitié, Paris, France.
Eric
E
Bruckert
INSERM UMRS 1166 ICAN, Université Pierre et Marie Curie Paris 6, Hôpital de la Pitie, Paris, France.
Martin John
MJ
Chapman
INSERM UMRS 1166 ICAN, Université Pierre et Marie Curie Paris 6, Hôpital de la Pitie, Paris, France.
Anatol
A
Kontush
D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood; D002788:Cholesterol Esters / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D018752:Diet, Fat-Restricted; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D015444:Exercise; D005260:Female; D006801:Humans; D008019:Life Style; D008075:Lipoproteins, HDL / Q000378:metabolism*; D053440:Lipoproteins, HDL3 / Q000032:analysis; D008077:Lipoproteins, LDL / Q000737:chemistry; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000175:diagnosis*; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D015397:Program Evaluation; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D002788:Cholesterol Esters; D008078:Cholesterol, LDL; D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; D008077:Lipoproteins, LDL; D014280:Triglycerides; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost
Antioxidative activity; High-density lipoprotein; Lifestyle intervention; Metabolic syndrome; Oxidative stress