Influence of IL1B, IL6 and IL10 gene variants and plasma fatty acid interaction on metabolic syndrome risk in a cross-sectional population-based study.

BACKGROUND & AIMS: Metabolic syndrome (MetS) is a cluster of interrelated risk factors for type 2 diabetes mellitus, and cardiovascular disease, with underlying inflammatory pathophysiology. Genetic variations and diet are well-known risk factor for MetS, but the interaction between these two factors is less explored. The aim of the study was to evaluate the influence of interaction between SNP of inflammatory genes (encoding interleukin (IL)-6, IL-1ß and IL-10) and plasma fatty acids on the odds of MetS, in a population-based cross-sectional study. METHODS: Among participants of the Health Survey - São Paulo, 301 adults (19-59 y) from whom a blood sample was collected were included. Individuals with and without MetS were compared according to their plasma inflammatory biomarkers, fatty acid profile, and genotype frequency of the IL1B (rs16944, rs1143623, rs1143627, rs1143634 and rs1143643), IL6 (rs1800795, rs1800796 and rs1800797) and IL10 (rs1554286, rs1800871, rs1800872, rs1800890 and rs3024490) genes SNP. The influence of gene-fatty acids interaction on MetS risk was investigated. RESULTS: IL6 gene SNP rs1800795 G allele was associated with higher odds for MetS (OR = 1.88; p = 0.017). Gene-fatty acid interaction was found between the IL1B gene SNP rs116944 and stearic acid (p inter = 0.043), and between rs1143634 and EPA (p inter = 0.017). For the IL10 gene SNP rs1800896, an interaction was found for arachidonic acid (p inter = 0.007) and estimated D5D activity (p inter = 0.019). CONCLUSION: The IL6 gene SNP rs1800795 G allele is associated with increased odds for MetS. Plasma fatty acid profile interacts with the IL1B and IL10 gene variants to modulate the odds for MetS. This and other interactions of risk factors can account for the unexplained heritability of MetS, and their elucidation can lead to new strategies for genome-customized prevention of MetS.

Effect of classic ketogenic diet treatment on lipoprotein subfractions in children and adolescents with refractory epilepsy.

OBJECTIVE: The aim of this study was to evaluate the effects of the classic ketogenic diet (KD) on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions in children and adolescents with refractory epilepsy. METHODS: This prospective study recruited children and adolescents of either sex, whose epilepsy was refractory to treatment with multiple drugs. To be included, the patient had to have an indication for treatment with the KD and be treated as an outpatient. At baseline and after 3 and 6 mo of the KD, lipid profile (total cholesterol [TC], triacylglycerols [TG], LDL cholesterol [LDL-C], and HDL cholesterol [HDL-C]), apolipoproteins (apoA-I and apoB), 10 subfractions of HDL, 7 subfractions of LDL, LDL phenotype, and LDL size were analyzed using the Lipoprint system. RESULTS: The lipid profile components (TC, TG, LDL-C, HDL-C, apoA-I, and apoB) increased during the 3-mo follow-up, and remained consistent after 6 mo of treatment. Similarly, non-HDL-C, TC/HDL-C, LDL-C/HDL-C, and apoB/apoA-I ratios, representing atherogenic particles, significantly increased. In contrast, qualitative lipoprotein characteristics progressively changed during the follow-up period. Small LDL subfractions increased, and this profile was related with reduced LDL size (27.3 nm to 26.7 nm). The LDL phenotype became worse; 52.1% of the patients had a non-A phenotype after 6 mo of the KD. Small HDL subfractions decreased only after 6 mo of the KD. CONCLUSIONS: KD treatment promotes negative changes in lipoprotein size and phenotype, contributing to atherogenic risk in these patients.

Influence of adiponectin gene variants and plasma fatty acids on systemic inflammation state association-A cross-sectional population-based study, São Paulo, Brazil.

SCOPE: Interactions between adiponectin genetic variants and plasma fatty acid profile can modulate plasma inflammatory biomarker concentration and the risk for metabolic diseases. The aim of this study was to investigate the interaction between single nucleotide polymorphisms of the adiponectin gene and plasma fatty acid profile in modulating the odds for systemic inflammation in a cross-sectional population-based study. METHODS AND RESULTS: Inflammatory patterns comprised 11 inflammatory biomarkers. Among participants of the Health Survey of São Paulo, 262 adults (19-59 years) met the inclusion criteria. Anthropometric parameters, blood pressure, plasma inflammatory biomarker concentration, and fatty acid profile were measured and five single nucleotide polymorphisms of the adiponectin gene (rs2241766, rs1501299, rs16861209, rs17300539, and rs266729) genotyped. Individuals in the upper 50th percentile for plasma araquidonic acid, n-3 highly unsaturated fatty acid and estimated delta-5-desaturase activity, had reduced odds of being in the inflammatory cluster (OR (95% CI) = 0.55 (0.32-0.95), 0.50 (0.28-0.88) and 0.48 (0.28-0.83), respectively). Gene-plasma fatty acid profile interaction was found between rs2241766 and n-3 (p = 0.019), rs16861209 and araquidonic acid and docosapentaenoic acid (p = 0.044, p = 0.037, respectively), and rs17300539 and saturated fatty acid (p = 0.019). CONCLUSION: Plasma fatty acid profile can interact with adiponectin gene variants to modulate the risk for systemic inflammatory state.

FISH OIL AND VITAMIN E CHANGE LIPID PROFILES AND ANTI-LDL-ANTIBODIES IN TWO DIFFERENT ETHNIC GROUPS OF WOMEN TRANSITIONING THROUGH MENOPAUSE.

BACKGROUND: studies have investigated the relationship between the transition through menopause and cardiovascular diseases. White population, generally, have lower levels of traditional coronary heart risk factors, particularly dyslipidemia, hypertension, obesity, and diabetes, and lower rates of coronary heart disease mortality, than black population. Furthermore many studies have shown the cardioprotective and anti-inflammatory effects of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) of marine origin. The aim of this study was to investigate the effect of omega-3 supplementation, combined or not with vitamin E, on oxidative biomarkers and lipid profiles in nonwhite and white women with dyslipidemia transitioning through menopause. METHODS: a randomized, double-blind, placebo-controlled trial was conducted. Seventy-four eligible women were assigned to receive: fish oil, fish oil plus vitamin E and placebo for three months. At baseline, 45 and 90 days blood sample for biochemical variables and biomarkers of oxidative stress were taken. Socioeconomic and lifestyle variables were collected with standardized questionnaires. RESULTS: after 90 days the fish oil plus vitamin E treated group had a significant decrease in total cholesterol and LDL-C. Furthermore, there was a decrease in anti- LDL- autoantibodies after 45 days. Plasma TBARS concentrations were increased after 90 days in the group receiving only fish oil when compared to the placebo and fish oil-vitamin E groups. All of the effects observed were independent of ethnic group. CONCLUSION: supplementation with fish oil and vitamin E reduced total cholesterol and LDL-C, but had opposite effects on oxidative stress compared to supplementation with fish oil alone.

Introducción: diversos estudios han investigado la relación entre la transición a la menopausia y las enfermedades cardiovasculares. Generalmente, la población de etnia blanca posee bajos niveles de factores de riesgo coronarios, particularmente dislipidemia, hipertensión, obesidad, diabetes y bajas tasas de mortalidad por enfermedades del corazón en comparación con la población de etnia negra. Además, varios estudios demostraron efectos cardioprotectores y antiinflamatorios provenientes de ácidos grasos poliinsaturados omega-3 (ácido eicosapentaenoico y ácido docosahexaenoico) de origen marino. El objetivo del estudio fue investigar el efecto de la suplementación de omega-3 combinado o no con vitamina E en biomarcadores oxidativos y perfiles lipídicos en mujeres blancas y no blancas con dislipidemia en transición hacia la menopausia. Métodos: fue realizado un estudio randomizado, duplo- ciego, placebo-controlado. Setenta y cuatro mujeres elegibles fueron escogidas para recibir: aceite de pescado, aceite de pescado con vitamina E y placebo durante tres meses. Fueron recogidas muestras de sangre en de referencia, 45 y 90 días para realizar exámenes bioquímicos y de biomarcadores para estrés oxidativo. Las variables socioeconómicas y de estilo de vida fueron recogidas por medio de cuestionarios estandarizados. Resultados: después de 90 días, el grupo tratado con aceite de pescado con vitamina E tuvo una disminución significativa para colesterol total y LDL-C. Además, hubo una disminución de anticuerpos anti-LDL después de 45 días. La concentración de plasma TBARS aumentó después de 90 días en el grupo que recibió solamente aceite de pescado, comparado con los grupos placebo y aceite de pescado con vitamina E. Todos los efectos observados fueron independientes del grupo étnico. Conclusión: la suplementación con aceite de pescado y vitamina E redujo el colesterol total y LDL-C, pero tuvo un efecto opuesto en el estrés oxidativo comparado con la suplementación solamente con aceite de pescado.

Soy isoflavones reduce electronegative low-density lipoprotein (LDL(-)) and anti-LDL (-) autoantibodies in experimental atherosclerosis.

BACKGROUND: Isoflavones present in soybean may contribute to soy atheroprotective effects. AIM OF THE STUDY: To investigate the effect of soy isoflavones supplementation on the formation of electronegative LDL (LDL(-)) and its autoantibodies in blood plasma and aortic atheromas of rabbits fed an atherogenic casein-based diet enriched with isoflavones. METHODS: New Zealand male rabbits (n = 15) were fed an atherogenic diet (27% casein) supplemented with isoflavones (0.73 or 7.3 mg of isoflavones/kg/day, Low and High Iso groups, respectively) for 180 days. Monthly, blood samples were collected after 12-15 h fasting and at 180 days of treatment all animals were sacrificed. Isoflavones were analyzed in plasma and urine samples by HPLC. LDL(-) in plasma and atheromas was detected by ELISA and immunohistochemistry, respectively, with a monoclonal antibody reactive to LDL(-). Autoantibodies reactive to LDL(-) were analyzed in plasma and aorta by ELISA. RESULTS: Low and High Iso groups had decreased LDL-cholesterol, increased HDL-cholesterol and lower levels of LDL(-) in blood plasma and aortic atherosclerotic lesions than the non-supplemented Control group. IgG autoantibodies reactive to LDL(- )were higher in plasma of the Control group in comparison with the High and Low Iso groups. In contrast, the aortas from animals that consumed isoflavones showed higher levels of IgG reactive to LDL(- )than the Control group. CONCLUSION: Soy isoflavones showed hypolipidemic effects and decreased the pro-inflammatory LDL(-) subfraction in blood plasma and aorta of hypercholesterolemic rabbits.