Molecular Characterisation of Lipid Droplet Function (2007–2009)
Fat is stored inside cells in spherical structures called lipid droplets. The accumulation of fat within lipid droplets underlies obesity. This project aims to understand how fat is stored within lipid droplets and how it is released when energy is required. In particular, we will look at two types of protein which move to lipid droplets under certain energy conditions and attempt to unravel how these proteins control fat storage and release. The first protein we will study, caveolin, normally associates with regions of the cell surface but moves to lipid droplets when cells are fed lipids. Mice which lack this protein eat more food but remain leaner than normal mice. Understanding how caveolin moves to lipid droplets and how it controls fat accumulation will therefore provide new insights into obesity and conditions associated with obesity, such as diabetes. The second protein to be studied, Rab18, is a member of a protein family which controls membrane movement within cells. Rab18 moves to lipid droplets when lipid release is stimulated. Therefore studies of Rab18 can provide new insights into the way lipids are released from fat tissue under conditions of starvation. The project will provide fundamental new insights into the basic mechanisms by which we store energy and the energy imbalances which cause obesity and related diseases.