Understanding the role of the intestinal melanocortin-4 receptor in the control of body weight

Advancements in obesity treatment with glucagon-like peptide-1 receptor agonists have led to substantial weight loss and reduced risk of comorbidities. An emerging target for obesity therapeutics is the gastrointestinal tract, which is the site of digestion and anorexigenic hormone secretion. The melanocortin-4 receptor (MC4R) is expressed on intestinal cells responsible for secretion of these hormones. In this thesis, we determined how intestinal MC4R affects energy balance and glucose tolerance in mice. Additionally, we confirmed peptide-YY secretion as a key mechanism of intestinal MC4R action. These findings provide evidence of a functional intestinal melanocortin pathway which influences appetite and weight.