The fat mass and obesity-associated (FTO) gene variant rs9939609 predicts long-term incidence of cardiovascular disease and related death independent of the traditional risk factors.

OBJECTIVE AND METHODS: The impact of the rs9939609 FTO variant on cardiovascular events was investigated in the 19-year follow-up of subjects recruited to the OPERA study. RESULTS: A total of 212 cardiovascular disease (CVD) and 152 coronary heart disease (CHD) events or deaths occurred during follow-up. The logistic regression analysis revealed that among the AA genotype the incidence of CHD (OR 1.905; 95% CI 1.250-2.903, p = 0.001) and CVD (OR 1.849; 1.265-2.702, p = 0.003) events or death was significantly higher when adjusted for age, sex, and study group. After further adjustment with BMI, smoking status, systolic blood pressure, and low-density lipoprotein cholesterol, the higher incidence of CHD and CVD events or death among subjects with the AA genotype remained significant (OR 1.895; p = 0.002 and p = 0.004, respectively). In Cox regression analysis, the AA genotype displayed a higher rate of CVD and CHD death when the model was adjusted for sex, age, and study group (p = 0.006 and p = 0.046). FTO rs9939609 AA genotype improved the C-index of the final predictive model from 0.709 to 0.715. In reclassification analyses, the integrated discrimination index was significant 0.011 (p = 0.010). CONCLUSION: The AA genotype of FTO rs9939609 seems to be associated with a higher risk of CVD, and this phenomenon seems to be independent of the traditional risk factors for atherosclerosis.

Resistin is an indicator of the metabolic syndrome according to five different definitions in the Finnish Health 2000 survey.

BACKGROUND: Resistin is a peptide hormone secreted mainly from human monocytes and macrophages. It has an unclear association with the metabolic syndrome, which is a cluster of cardiovascular risk factors such as glucose intolerance, central obesity, insulin resistance, dyslipidemia, and hypertension. We examined the association of resistin with metabolic syndrome and its components in a population-based cohort. METHODS: A subsample of a large Finnish cross-sectional health examination survey (the Health 2000 Survey) was studied. Resistin was measured using an in-house assay based on the DELFIA® technique in 1,508 Finnish men and women aged 45-74 years. Metabolic syndrome was defined according to five different definitions. RESULTS: Resistin levels were higher in the subjects with metabolic syndrome when compared to the subjects without metabolic syndrome (P < 0.05 for every metabolic syndrome criterion). In logistic regression analysis, a high resistin level was an independent predictor of the prevalence of metabolic syndrome (P < 0.05 for every criterion). Resistin was positively associated with waist circumference, tumor necrosis factor-α, and insulin resistance assessed by the homeostasis model and inversely with total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol after adjusting for age, gender, and body mass index (P < 0.05 for all). CONCLUSIONS: These results clarify the controversial association of resistin in obesity and metabolic syndrome, suggesting that a high resistin level is associated with clustering of metabolic disturbances.

The effect of energy restriction during pregnancy on obesity-related peptide hormones in rat offspring.

It has been proposed that fetal exposure to environmental stressors, such as undernutrition, during critical periods of development may lead to adaptations that permanently change the structure and function of the body. These adaptations may be important for immediate survival during fetal development, but can predispose to disease in later life. We designed a pilot study investigating the effect of fetal undernutrition on the obesity-related peptides adiponectin, ghrelin, leptin and resistin levels in rat. We also wanted to explore changes in lipid and insulin metabolism. Sprague-Dawley rats were randomly assigned to three dietary treatment groups on day 4 of gestation. The control group was fed ad libitum and the food-restricted rats received either 75% or 50% of ad libitum food intake until parturition. Serum levels of obesity-related peptides as well as lipid and insulin levels were measured from 1-month-old pups. Serum resistin concentrations were higher in both food-restricted groups and serum adiponectin concentration was lower in the 50% food-restricted group compared to the control group. Serum total cholesterol levels were significantly higher in both food-restricted groups. These results indicate that undernutrition during fetal development may lead to unfavorable changes in obesity-related peptide hormones as well as evoking adverse changes in serum cholesterol levels. The observed changes may predispose to insulin resistance and significantly increase the risk of developing cardiovascular disease in later life.