Ashford, Michael

Chronic obesity is currently at epidemic levels in the UK and many other countries worldwide and is having a major adverse impact on our society. It is estimated that more 25% of the adult population are obese and around two thirds are either overweight or obese.  Worryingly over the last 20 years there has been a ~3 fold increase in the number of children and adolescents who are obese or overweight. This trend is alarming, as chronic obesity is associated with increased risk of cardiovascular and liver disease and some cancers. Most notably however, obesity is a primary driver for induction of peripheral insulin resistance, which when coupled with pancreatic beta cell functional insufficiency, leads to diabetes. Recent work also indicates that the risk of Alzheimer’s disease is higher in patients with diabetes and obesity. Therefore it is clear that our society is on a trajectory that will see significant increases in the proportion of individuals entering or in old age with severe chronic health issues. This places an enormous burden on the NHS and society generally, which is likely to worsen over the next 10-20 years if effective actions are not taken soon.

The aim of our work is to understand, at a molecular level, why and how these diseases are linked, in order to find new ways to prevent their long-term harmful consequences. We currently use a number of different systems to study the interactions between the hormones, leptin and insulin, and glucose and fat metabolism. Our current research projects are addressing: (i) how the enzyme beta secretase (BACE1) influences nutrient metabolism and leptin and insulin sensitivity; (ii) the role of the transcription factor, Nrf2, on glucose and lipid metabolism; (iii) how different cellular stresses influence cell metabolism and function; and (iv) how hypothalamic neurons and pancreatic beta cells sense changes in glucose levels.