Sorting apples from pears: do Wnt proteins determine body fat distribution?

Dissecting the role of Wnt signalling in the regulation of fat distribution and susceptibility to cardiometabolic disease

BHF Intermediate Clinical Research Fellow Dr Constantinos Christodoulides is working out if proteins called Wnts affect a person’s risk of developing heart and circulatory disease. The location of body fat determines how it influences the risk of heart and obesity-related disease. For instance, build-up of fat in the abdomen and chest (an ‘apple shaped’ body type) increases the risk of heart and metabolic disease, whereas fat around the hips, thighs and bottom (a pear shaped body type) may be protective. The different effects of body fat on health have long puzzled scientists, but we now know that one reason is that fat cells from upper and lower body areas are different. Fat deposits originate from ‘master’ cells called adipose progenitor cells, which develop into mature fat cells (adipocytes) with different properties. Growth factor proteins called Wnts are important in determining fat distribution and body shape. Dr Christodoulides believes Wnts help to establish the identity of adipose progenitor cells, and whether they will become upper or lower body type fat cells. In this project, he will study how Wnts control fat distribution by examining the body shape of people with faulty Wnt pathway genes. He will measure blood pressure, circulating fat levels and heart risk scores in these people to see if there is a correlation between heart health and faulty Wnt genes. He will examine the effects of switching Wnt genes on and off on human fat cell behaviour in the lab, and on fat cell growth in zebrafish. This research will work out how Wnts are involved in fat cell growth and function throughout the body, and in determining body shape and heart disease risk. It could reveal new ways to prevent and treat heart disease and diabetes by turning 'bad' upper-body fat into 'good' lower-body fat.