Reference
Singh, A., Haq, N., Yang, M., Luckey, S., Mansouri, S., Campbell-Thompson, M., Jin, L., Christou-Savina, S., & Lartigue, G. de. (2025). Transcriptome-guided GLP-1 receptor therapy rescues metabolic and behavioral disruptions in a Bardet-Biedl Syndrome mouse model. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI184636
Info
FirstAuthor:: Singh, Arashdeep
Author:: Haq, Naila
Author:: Yang, Mingxin
Author:: Luckey, Shelby
Author:: Mansouri, Samira
Author:: Campbell-Thompson, Martha
Author:: Jin, Lei
Author:: Christou-Savina, Sofia
Author:: Lartigue, Guillaume de
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Title:: Transcriptome-guided GLP-1 receptor therapy rescues metabolic and behavioral disruptions in a Bardet-Biedl Syndrome mouse model
Year:: 2025
Citekey:: SinghEtAl_2025_TranscriptomeguidedGLP1Receptor
itemType:: journalArticle
Journal:: The Journal of Clinical Investigation
DOI:: 10.1172/JCI184636
Link
Abstract
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Glucagon-like peptide-1R agonist (Semaglutide) promotes hypophagia3 induced weight loss and improves nesting behavior and glucose tolerance in 4 adult Bbs5 null mice.
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iliopathy characterized by obesity, hyperphagia, and 3 learning deficits, arises from mutations in Bbs genes
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BBSome, a complex regulating primary cilia 5 function
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Bbs5-/- mice displayed hyperphagia, learning 7 deficits, glucose/insulin intolerance, and disrupted metabolic hormones, phenocopying 8 human BBS
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unique immunophenotype in white adipose tissue with 9 increased proinflammatory macrophages and dysfunctional regulatory T cells, 10 suggesting a distinct mechanism for adiposity compared to typical obesity models
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Hypothalamic transcriptomics 13 revealed dysregulated endocrine signaling pathways with functional analyses confirming 14 defects in insulin, leptin, and cholecystokinin (CCK) signalling, while preserving 15 glucagon-like peptide-1 receptor (GLP-1R) responsiveness. Notably, treatment with a 16 GLP-1R agonist effectively alleviated hyperphagia, body weight gain, improved glucose 17 tolerance, and circulating metabolic hormones in Bbs5-/- mice.