Insulin Modulation of fMRI Connectivity and Food Reward

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 DESCRIPTION (provided by applicant): Insulin is a hormone released by the pancreas in response to increases in glucose levels that result from food intake. In addition to stimulating glucose uptake in the periphery, insulin signals the central nervous system to induce satiety and inhibit feeding behavior. Previous studies have compared brain responses to palatable food receipt across obese and lean individuals, or through the ingestion of a mixed meal. However, obesity is a complex metabolic state, and a mixed meal preload induces changes in a variety of hormones. Furthermore, it is unknown how insulin resistance may alter the ability of circulating insulin to affect brain activity. The current study builds upon a K01 project that is comparing brain responses to palatable food across insulin resistant and healthy individuals, during fasting and after a mixed meal preload. Initial findings show that following a meal, insulin resistant individuals show a hyper-reactivity of the striatum - a network involved in reward - relative to healthy controls. To begin to identify the mechanistic basis of these findings, the current study will recruit healthy participants who will undergo two functional magnetic resonance imaging scans. One scan will be performed in the fasted state, and the alternate scan will be conducted during an isoglycemic hyperinsulinemic clamp. This project will allow us to identify the specific effects of circulating insulin on brain reactivity to palatable food. We will also use state of theart functional imaging techniques to identify how insulin affects the functional connectivity between brain regions, particularly those in the striatum. The study team includes Dr. Howard Aizenstein, an expert in functional and structural neuroimaging, Dr. Frederico Toledo, a clinical endocrinologist with years of experience in implementing and interpreting clamp studies, and Dr. John Ryan (PI), a neuroscientist who specializes in the effects of diabetes on the brain. This work will bridge the findings of the K01 project and lay the groundwork for future studies in insulin resistant individuals to identify how insulin resistance in the brain may alter the abilityof peripheral hormones to provide appropriate feedback signals.