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.

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.

Nutrient-adjusted high-fat diet is associated with absence of periepididymal adipose tissue inflammation: is there a link with adequate micronutrient levels?

The aim of this study was to investigate the real impact of dietary lipids on metabolic and inflammatory response in rat white adipose tissue. Male healthy Wistar rats were fed ad libitum with a control diet (CON, n=12) or with an adjusted high-fat diet (HFD, n=12) for 12 weeks. Oral glucose and insulin tolerance tests were performed during the last week of the protocol. Plasma fatty acid, lipid profile, body adiposity, and carcass chemical composition were analyzed. Plasma concentration of leptin, adiponectin, C-reactive protein (CRP), TNF-α, IL-6, and monocyte chemotactic protein (MCP-1) was measured. Periepididymal adipose tissue was employed to evaluate TNF-α, MCP-1, and adiponectin gene expression as well as NF-κB pathway and AKT proteins. Isocaloric intake of the adjusted HFD did not induce hyperphagia, but promoted an increase in periepididymal (HFD = 2.94 ± 0.77 vs. CON = 1.99 ± 0.26 g/100 g body weight, p = 0.01) and retroperitoneal adiposity (HFD = 3.11 ± 0.81 vs. CON = 2.08 ± 0.39 g/100 g body weight, p = 0.01) and total body lipid content (HFD = 105.3 ± 20.8 vs. CON = 80.5 ± 7.6 g carcass, p = 0.03). Compared with control rats, HFD rats developed glucose intolerance (p=0.01), dyslipidemia (p = 0.02) and exhibited higher C-reactive protein levels in response to the HFD (HFD = 1002 ± 168 vs. CON = 611 ± 260 ng/mL, p = 0.01). The adjusted HFD did not affect adipokine gene expression or proteins involved in inflammatory signaling, but decreased AKT phosphorylation after insulin stimulation in periepididymal adipose tissue (p = 0.01). In this study, nutrient-adjusted HFD did not induce periepididymal adipose tissue inflammation in rats, suggesting that the composition of HFD differently modulates inflammation in rats, and adequate micronutrient levels may also influence inflammatory pathways.