Should GLP-1 receptor agonist therapy be used to treat obesity in Bardet-Biedl syndrome?

Bardet-Biedl syndrome (BBS) is a complex genetic condition that can affect multiple organ systems, frequently causing pigmentary retinopathy, renal abnormalities, polydactyly, and obesity. Metabolic disturbances including obesity, unsuppressed appetite, and an increased risk of type 2 diabetes (T2D) present clinical management challenges. In this issue of the JCI, Singh et al. present a mouse model of a specific BBS subtype with genetic deletion of the Bbs5 gene. The model recapitulates many of the clinical features observed in patients living with BBS5 and sheds light on adipocyte biology, as well as the hypothalamic mechanisms driving hunger- and food-seeking behaviors that fuel the adverse metabolic phenotype. Importantly, exogenous GLP-1 receptor agonist treatment suppressed both appetite and weight, opening opportunities for direct translation into the clinical setting.