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Abstract:
Exenatide is a glucagon-like peptide-1 (GLP-1) analog, used in clinical practice for treatment of type-2-diabetes. It increases energy intake and reduces body weight in long-term treatment in humans, but the underlying
physiological mechanisms are still unclear. To investigate its central nervous effects we performed functional magnetic resonance imaging (fMRI) in 20 male obese (body mass index 28.4 - 42.8 kg/m², mean 34.6 kg/m²; age 20 - 47 years, mean 28 years) while intravenously administrating exenatide. Infusion rate was 0.12 pmol/kg/min., total duration of infusion was 2.5 hours, the study design was cross-over, placebo controlled, double-blind and randomized. Inside the scanner subjects rated pictures of food regarding their tastiness. We used a recently published parameter-free method called ‘eigenvector centrality mapping’ (ECM) for assessing functional con-
nectivity in each voxel (Lohmann et al. 2010). ECM attributes a centrality value to each voxel reflecting its degree of connectedness. Results showed a statistically significant global maximum for higher centrality (which
suggests a higher connectivity) in hypothalamus in the exenatide condition compared to placebo. The hypothalamus is a key region for the control of energy homeostasis, where from animal data it is known that GLP-1 receptors are present and involved in regulation of energy uptake. Our results demonstrate that peripherally administered exenatide mediates centrality in food-related networks. This shows for the first time a modulation of central
networks regulating energy homeostasis after exenatide infusion and suggests a central nervous mechanism for the reduction of energy intake under influence of exenatide.
