Thomas J. Baranski, M.D., Ph.D.
Project Overview:
Diabetes and obesity have become epidemic and significantly impact healthy lifespans. Much attention has focused on medical therapies to treat insulin resistance and obesity, but there continues to be a great need for safe and effective treatments. Nutritional approaches hold great promise and recent studies in rodents and humans demonstrate promise for citrulline supplementation. The mechanisms of the beneficial effects of citrulline remain unknown. We have performed studies of citrulline supplementation in a model of diet-induced insulin resistance in Drosophila. We have previously demonstrated high sugar diets induce phenotypes in flies consistent with insulin resistance: elevated glucose levels, increase in adiposity, decreased insulin signaling, increased free fatty acids, and decreased longevity. Citrulline supplementation completely rescued the increase in body fat and also improved the hemolymph glucose levels. The mechanisms by which this occur are unknown and are the focus of this proposal. We will take advantage of the genetic power of the Drosophila model to understand why citrulline is beneficial.
We propose two aims: 1. Dissect the molecular mechanisms by which citrulline supplementation has beneficial effects on glucose and lipid metabolism, and 2. Explore the impact of genetic background on citrulline response. Insights from these studies will help direct the types of clinical trials that will be employed in human studies and will guide personalized medical approaches for citrulline therapy.
