Project description
Cardiometabolic risk factors in obesity
The increase in obesity rates in the human population worldwide is a major threat to public health systems. The main healthcare costs are due to cardiometabolic impairments such as insulin resistance, high cholesterol and hypertension, which increase the risk of type 2 diabetes and cardiovascular disease. Curiously, some obese individuals are resistant to cardiometabolic complications, while some normal weight individuals suffer from comorbidities usually linked to obesity. Recent genome studies have identified multiple genetic loci associated with increased subcutaneous and overall body fat deposition but lower cardiometabolic risks. The primary goal of the EU-funded GeneLifeCard project is to examine if genetic and lifestyle factors abolish the impact of long-term weight gain on cardiometabolic risk. The study will be carried out through meta-analyses (the statistical analysis combining results of multiple studies) of five different cohorts with repeated measures of body weight and cardiometabolic traits.
Objective
The current obesity pandemic is a major threat to public health systems worldwide. The majority of obesity-related health care costs are due to cardiometabolic impairments such as insulin resistance, dyslipidemia, and hypertension, which increase the risk of type 2 diabetes and cardiovascular disease. However, many obese individuals seem resistant to cardiometabolic complications, the “metabolically healthy obese (MHO)”, while some normal weight individuals suffer from comorbidities similar to the obese. Genetic mechanisms may partly explain this paradox. Recent genome-wide studies have identified multiple genetic loci associated with increased overall body fat and subcutaneous fat deposition but lower cardiometabolic risk. Vice versa, the fat-decreasing alleles at these loci are associated with higher cardiometabolic risk. Some lifestyle factors, such as higher physical activity and smoking, are associated with lower body fat but show directionally opposite effects on cardiometabolic risk. At present, it remains unclear whether genetic predisposition to higher subcutaneous fat storage or healthy lifestyle behaviors may uncouple long-term weight gain from cardiometabolic risk during adulthood. Thus, the primary aim of the present project is to examine whether genetic and lifestyle factors abolish the impact of long-term weight gain on cardiometabolic risk by meta-analyses of five prospective cohorts with repeated measures of body weight and cardiometabolic traits. I will also examine whether these factors predict a MHO status in middle-age and the maintenance of such status over time. My results will provide new biological insights and may enable targeted lifestyle interventions against obesity-related cardiometabolic impairments. Moreover, the project will greatly advance my career by allowing me to learn highly valuable research skills in the area of genetic epidemiology, complementing my previous expertise in the field of cardiovascular epidemiology.
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Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
1165 Kobenhavn
Denmark