Anders Englund, MD

University of Copenhagen, Faculty of Health Sciences

Title of project

LEAP2 – appetite regulation and glucose metabolism in obesity

Abstract

The global prevalence of obesity continues it surge resulting in increased individual and societal burdens. Lack of prevention strategies and limited and short-lasting effects of lifestyle interventions call for novel effective and durable pharmacotherapeutics. Recently, the naturally occurring peptide, liver-enriched antimicrobial peptide 2 (LEAP2), has gained interest due to its reciprocal relationship with the hunger hormone ghrelin. The aim of the present PhD project is to investigate appetite regulating and metabolic effects of LEAP2 in obesity in three clinical sub-studies. All sub-studies will be performed in obese individuals and are designed as randomized, double-blind, placebo controlled, crossover studies involving two experimental days receiving LEAP2 and placebo infusion, respectively. We will investigate LEAP2’s effect on: 1) postprandial physiology and ad libitum food intake; 2) neural activity in brain regions involved in food reward assessed through functional magnetic resonance imaging (fMRI) and, 3) dynamic simultaneous total-body (TB) glucose metabolism using TB positron emission tomography (PET)/computed tomography (CT) scans. Compared to placebo, we hypothesize that LEAP2 improves postprandial glucose tolerance, reduces ad libitum food intake, reduces neural activity in brain regions involved in food reward, and increases hepatic, intestinal and/or skeletal muscle glucose uptake. With this innovative interdisciplinary PhD project, we combine clinical and imaging sciences to delineate the effects of LEAP2 in obesity and build the foundation for future pharmacological studies investigating LEAP2-based therapeutics for obesity and other metabolic diseases.

Anders Englund, MD
Principal supervisor

Filip Krag Knop, Gentofte Hospital, Center for Clinical Metabolic Research

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