GeneLifeCard · Genetic and lifestyle regulators of cardiometabolic risk in individuals gaining weight
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2020-09-01 → 2022-08-31
- EU contribution
- €207,312
- Participants
- 1
- Scheme
- MSCA-IF
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Results in brief
Genetic and lifestyle regulators of cardiometabolic risk in individuals gaining weight
Obesity it is clearly a current public health issue. The prevalence of obesity has tripled in children and adults in the last 30 years, and there are more than 50% of overweight adults in Europe. Obesity is a major risk factor for type 2 diabetes and cardiovascular disease. Even though most obese individuals have an increase disease risk, as many as 10-40% of obese individuals, often termed “metabolically healthy obese”, do not have an increased risk as compared to metabolically unhealthy individuals (see figure). We hypothesized that the expandability of subcutaneous fat may be at play in this paradox. Meaning that the ability to store fat subcutaneously may protect from fat being stored ectopically in non-adipose tissues such as visceral fat (e.g. heart and pancreas), where it leads to lipotoxic effects. Genetic factors play an important role in the ability to expand subcutaneous fat stores and one of the main interests of this proposal is to identify genetic loci associated with higher overall body fat and fat storage on the hip, yet an improved disease risk profile for cardiometabolic conditions. Thus, the overall objective of the present proposal is to examine whether genetic predisposition to higher fat expandability or healthier lifestyle behaviors diminishes the impact of long-term weight change on risk of cardiometabolic disease. We do this by analyzing individuals from Danish and United Kingdom prospective studies, with data available on genetics, blood markers, cardiovascular and type 2 diabetes disease occurrence and follow-up of body weight change. The findings on the effects of genetic variation and lifestyle (i.e., physical inactivity and smoking) may improve understanding of the biological mechanisms that link adiposity to cardiometabolic health. The relevance for society will be that these findings may open new understanding for developing novel treatments with antidiabetic or anti-cardiovascular effects, but also potential public health recommendations for disease prevention.
Data: CORDIS, © European Union
Project 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.
Original text from CORDIS.
Participants
- KOBENHAVNS UNIVERSITET · KOBENHAVNCoordinatorDenmark
Links
Data: CORDIS, © European Union