Periodic Reporting for period 1 - GeneLifeCard (Genetic and lifestyle regulators of cardiometabolic risk in individuals gaining weight)
Okres sprawozdawczy: 2020-09-01 do 2022-08-31
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.
We found evidence that higher physical activity and decrease sedentary time associated with lower body weight and fat percentage in general. Meaning that physical inactivity was associated with lower body weight. We further provide bidirectional evidence of causality for the association between higher sedentary time and higher adiposity. This means that decreasing sedentary time is beneficial for weight management, but also that weight loss may help reduce sedentary time, forming a reinforcing loop. However, we found no clear evidence that higher physical activity associated with improve body fat distribution, meaning that we could not explain the hypothesis that higher fat expandability was associated with a healthier lifestyle.
In relation to smoking, our findings suggested that tobacco smoking associated with higher abdominal fat and that this came at the cost of lower gluteofemoral fat. Further that the effects were coming mostly from increase abdominal visceral adipose tissue rather than subcutaneous. Thus, our findings suggest that smoking has poor fat expandability properties. Thus, we speculate that a plausible explanation for the deleterious effects from smoking on cardiometabolic diseases may be due to a decrease fat expandability.
One of the aims of this proposal was to examine whether the genetic predispositions to higher fat expandability predict a metabolically healthy obese state in middle age and whether this state was sustained after 5-year period. Our analysis in this regard was inconclusive, most likely due to low statistical power. Thus, we could not conclude that higher genetic predisposition to higher fat expandability did not associate with metabolically healthy obese.
We show that children with low body size in childhood that then have a high body size as adults had the highest risk for type 2 diabetes. As expected, high body size in adulthood was a major risk factor for cardiometabolic disease, however body size in childhood was a risk determinant for type 2 diabetes, but not for cardiovascular disease. We speculate that lean children may have an increased susceptibility for type 2 diabetes because of a limited capacity for triglyceride storage in the adipose tissue (lower fat expandability), which may lead to metabolic complications upon weight gain due to lipotoxicity in adipose tissue and systematically.
The exploitation of the project was not possible due to COVID-19 restrictions. However, once these results are publicly available, anyone should have access to these open access results for applicability in any setting.
This project had also an impact in my personal career, training, and expanded my network and access infrastructure. I develop further skills like leadership, project management and communication. I expanded my publication list and research credibility in the field. All these training, experiences, networking and gained knowledge made of me a senior interdisciplinary researcher and I can humbly feel ready to become an independent leader in the short future.
This project will have a biological impact in the understanding of weight change, genetic predisposition to fat expandability and cardiometabolic risk that will pave the way for future research with translation impact. Further the public health implications of childhood and adulthood body size change in relation to the risk of cardiometabolic disease will be of relevance for disease prevention.