Transcriptome-guided GLP-1 receptor therapy rescues metabolic and behavioral disruptions in a Bardet-Biedl syndrome mouse model
Singh A., Haq N., Yang M., Luckey S., Mansouri S., Campbell-Thompson M.
Animal Study, published in J Clin Invest (2025) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Animal Study
- Journal
- J Clin Invest (2025)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 40233116
- PMCID
- PMC12165790
- DOI
- 10.1172/jci184636
- Citations
- 3
Abstract (original English)
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 but failed to normalize blood glucose, suggesting defective insulin action. Hypothalamic transcriptomics revealed dysregulation of endocrine signaling pathways, with functional analyses confirming defects in insulin, leptin, and cholecystokinin (CCK) signaling, while glucagon-like peptide-1 receptor (GLP-1R) responsiveness was preserved. Notably, treatment with a GLP-1RA effectively alleviated hyperphagia and body weight gain, improved glucose tolerance, and regulated circulating metabolic hormones in Bbs5-/- mice. This study suggests that Bbs5-/- mice represent a valuable translational model
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
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