Targeting inflammatory cells to reduce the risks of obesity

Targeting macrophage lipid metabolism to dissociate obesity from cardiovascular risk (renewal)

The release of fat from body fat tissue into the bloodstream is tightly regulated. However, in people who are overweight this regulation is disrupted and too much fat can be released into the blood and other tissues. When this happens, the fat can trigger inflammation, which in turn contributes to heart disease. In this programme, Professor Vidal Puig is studying cells called adipose tissue macrophages (ATMs). His team has previously shown that they play an important role in controlling the storage and release of fats from body fat tissues. Now, they will investigate three potential processes they believe link the control of fat levels by ATMs with inflammation. They will use mice with genetic alterations in fat tissue and ATMs to study 1) how abnormal fat cells direct fat molecules toward ATMs, 2) how defective communication by ATMs prevents the safe storage of fat molecules, and 3) how ATMs reorganise fat molecules incorrectly, making them toxic to surrounding tissues. They will also use human stem cells to see if the same processes happen in a human system. Through this work they hope to find new treatments that can reduce the harmful effects of obesity related inflammation - either by improving the way fat tissue regulates how fat is stored, or encouraging ATMs to store fat in safer ways or convert harmful fats into safer ones.