Approved research

Determinants of human fat distribution

Lay summary

Obesity is an escalating and significant contributor to mortality and morbidity in the UK and elsewhere. Obesity develops through the imbalance between energy intake and energy expenditure and most research today indicate that central regulation of food intake in a adverse and plentiful environment is the main reason for the imbalance leading to total body fat accumulation. However, the metabolic consequences of regional expansion of body fat depots show a highly interesting and dichotomous pattern: lower body fat accumulation is not associated with increased risk of type 2 diabetes or cardiovascular disease whereas upper body obesity is. There are some indications from the literature that the determinants of regional fat distribution is governed by genes important to tissue development and adipocyte cellularity. Most of this research has been conducted in large datasets but with poor quality assessment of body fat stores, typically waist and hip circumferences measured by tape measure. We intend to use the DXA imaging platforms in the UK Biobank to explore genetic and other determinant of lower vs upper body fat distribution to better understand the mechanisms by which lower body obesity protects against heart disease and type 2 diabetes. This research is in line with the stated aim of the UK Biobank 'the prevention, diagnosis and treatment of a wide range of life-threatening illnesses'. The first priority is to conduct a non-biased genome-wide search for associations between genotype data and body fat distribution parameters derived from the DXA imaging platform. Other cohorts, such as the Oxford Biobank (n=5,000), have similar measurements and this will support the research. As a second priority we would want to look for associations between nutritional and social parameters and body fat distribution to lay the foundation for epigenetic mechanisms governing body fat distribution. All participants taking part in the imaging platform. In the first instance we will use data from the 5000 people in the early release and when available analyse the entire data set.