Drug Discovery Opinion

The presence of multiple redundant and compensatory pathways controlling energy homeostasis has, so far, limited the effectiveness of anti-obesity treatments and suggests that combination therapy may be the best approach for treating the worldwide obesity epidemic. Writing in the journal Cell Metabolism, researchers at Merck have now demonstrated a role for the orphan bombesin receptor subtype 3 (BRS-3) in controlling energy balance.

Using a selective BRS-3 agonist (Bag-1) and antagonist (Bantag-1), the team have established a role for BRS-3 in the regulation of food intake, metabolic rate, and body weight. Intracerebroventricular infusion of the peptide Bantag-1 led to higher food intake and a progressive increase in adipose mass and body weight whereas oral administration of Bag-1 increased metabolic rate and reduced food intake, adipose weight, and body weight. Prolonged high levels of brain receptor occupancy by agonist increased weight loss, suggesting a lack of tachyphylaxis.

As well as suggesting a potential new target for the treatment of obesity, the discovery of selective BRS-3 agonists and antagonists will allow investigation of the mechanisms by which BRS-3 regulates energy metabolism as well as exploration of other aspects of BRS-3 biology.

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