Transcriptome-guided GLP-1 receptor therapy rescues metabolic and behavioral disruptions in a Bardet-Biedl syndrome mouse model.

ABSTRACT: Bardet-Biedl syndrome (BBS), a ciliopathy characterized by obesity, hyperphagia, and learning deficits, arises from mutations in Bbs genes. Exacerbated symptoms occur with mutations in genes encoding the BBSome, a complex regulating primary cilia function. We investigated the mechanisms underlying BBS-induced obesity using a Bbs5-knockout (Bbs5-/-) mouse model. Bbs5-/- mice were characterized by hyperphagia, learning deficits, glucose/insulin intolerance, and disrupted metabolic hormones, phenocopying human BBS. White adipose tissue in these mice had a unique immunophenotype, with increased proinflammatory macrophages and dysfunctional Tregs, suggesting a mechanism for adiposity distinct from those of typical obesity models. Additionally, Bbs5-/- mice exhibited pancreatic islet hyperplasia

SUBMITTER: Singh A 

PROVIDER: S-EPMC12165790 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature