Nimesh Mody & Matteo Zanda

Obesity and type-2 diabetes are increasingly prevalent, presenting a major public health challenge. These two closely associated medical conditions are reaching epidemic levels in many parts of the industrial world including Scotland.

Therefore, it is of vital importance to use new approaches to further our understanding of the complex connections between obesity and the development of type-2 diabetes. Vitamin A and vitamin A like molecules (called retinoids) have been shown to have major effects on body fat and blood glucose levels and thought to have a role in obesity. In particular, a retinoid drug called Fenretinide has been shown in my lab to partially prevent (or reduce) obesity and type-2 diabetes caused by feeding a high-fat diet in mice. Fenretinide is currently being tested in human clinical trials in obesity-related studies; however the link between Fenretinide and related retinoids, and obesity and diabetes is still not well understood. Fenretinide is particularly interesting as it appears to act through ways not related to vitamin A or other retinoids normally found in the body. In particular Fenretinide appears to block the production of ceramide, a lipid that has also been shown to play an important role in obesity and type-2 diabetes.

We aim to chemically modify Fenretinide to produce two different versions; one that will retain retinoid-like properties, whilst the other will be lacking them. We will compare the properties, characteristics and effects of these two compounds to see how similar they are to the original Fenretinide. Through these experiments, we aim to find out whether the beneficial effects of Fenretinide in safely reducing obesity and type-2 diabetes is due to retinoid-like properties.

This information will help us further our understanding of the complex connections between obesity and the development of type-2 diabetes and may help us to develop new drugs that are better at treating these medical conditions.