Inward Glucose Transfer Accounts for Insulin-Dependent Increase in Brain Glucose Metabolism Associated with Diet-Induced Obesity

Objective: There is a general agreement that there are changes in brain metabolism in insulin-resistant individuals during conditions of hyperinsulinemia. However, the impact on obesity is unclear, and the metabolic constants underlying these modifications are unknown. The aim of this study was to evaluate these changes in a large animal model of diet-induced obesity. Methods: Twenty adult miniature pigs were fed with either an obesogenic diet or a regular diet for 5 months. At that time, fat deposition was evaluated using computed tomography scanning, and 18fluorodeoxyglucose positron emission tomography images were acquired dynamically both in the fasted state and during a euglycemic-hyperinsulinemic clamp. Glucose uptake rates and pixel-wise modeled brain volumes were calculated together with brain connectivity. Results: Whole-body insulin sensitivity was reduced by more than 50% in the obesity group. During insulin stimulation, whole-brain insulin-induced increased glucose uptake was unaltered in lean animals but increased markedly in the animals with obesity. The increased glucose uptake reflected an increase in the inward transfer without changes in phosphorylation or outward brain transport. Connectivity was increased in the animals with obesity. Conclusions: Diet-induced obesity is associated with an increase in insulin-stimulated brain glucose uptake as a consequence of a larger inward transfer. These changes occurred together with an increased connectivity in reference to regions associated with memory recollection.