Causes and consequences of pathological adipose remodelling

The change in risk of diabetes, heart attacks and strokes that are caused by weight gain varies among people. Fat tissue is complex and variable among body regions and it is not well understood, but it appears that the way fat tissue responds to extra storage is important.

We will examine two rare, severe human genetic disorders. One is characterised by impaired copying and repair of genes producing fat loss under the skin, and the other has a defect in linking mitochondria (the cell’s power-generating organs) which produces dramatic accumulation of upper body fat. By studying people, cells and mice with the same gene changes, we will investigate how gene copying and repairing, and mitochondrial linkage keep fat tissue healthy and whether this malfunctions in disease. We will also use emerging techniques to study all possible changes in a gene simultaneously rather than one by one, starting with the insulin receptor.

Our findings will accelerate diagnosis of rare disease and it will add to our knowledge of gene changes in the general population.