Targeting the Hunger Hormone Receptor: Ghrelin Antagonists as Potential Therapeutics for Stress-Induced Binge Eating and Obesity

Progress is inherent in both solving old and new challenges. For example, the ability to create synthetic products not naturally occurring and their widespread availability, as well as high levels of everyday stress, contribute significantly to the extent of obesity. One of the contemporary targets in the treatment of both obesity and eating disorders that predispose individuals to their development, such as compulsive overeating and food addiction, is the receptor for the so-called “hunger hormone” ghrelin. With the benefit of molecular docking and molecular dynamics simulations, we calculated the binding energies of the ghrelin antagonists D-Lys3-GHRP-6 and YIL 781 and assessed their impact on chocolate consumption in rats under stress. In silico evaluations demonstrated greater affinity for YIL 781 than for D-Lys3-GHRP-6, which was in agreement with the experimental data. Therefore, a reduction in mean chocolate consumption in stressed rats after YIL 781 administration was demonstrated, and a theoretical model of the antagonist's interactions with the ghrelin receptor was developed for future studies.