Grant: Project Grant

Antipsychotic medications (AP) are used for treating schizophrenia. While effective they have harmful side effects such as causing weight gain and impairing how the body uses fat and sugar. The use of APs increases the risk of developing diabetes and cardiovascular disease and is one of the reasons why individuals with schizophrenia have a shorter lifespan than the general population. Treating the metabolic complications of APs has proven to be very challenging and new approaches to combat these side effects are needed. We have found that lifestyle interventions like exercise and the provision of ketogenic diets can protect against the metabolic consequences of APs in mice. Unfortunately, adherence to exercise and diet programs is poor in individuals take APs. Given this we have been using "lifestyle" interventions as a tool to identify new pathways that could be targeted to offset the harmful side effects of APs. Exercise and ketogenic diets increase the circulating level of a molecule called FGF21. We believe that using drugs which increase circulating FGF21 will alleviate the harmful metabolic complications of APs. We also hypothesize that FGF21 is a likely candidate mediating the beneficial effects of exercise against the metabolic effects of APs. Over the next 5 years we will test these hypotheses using a variety of different experiments in mice. The data generated from this project will provide important insight into new approaches that could be used to improve health in individuals taking APs.