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Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):1820-5. doi: 10.1073/pnas.0812518106. Epub 2009 Feb 3.

Transient ciliogenesis involving Bardet-Biedl syndrome proteins is a fundamental characteristic of adipogenic differentiation.

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1
Laboratoire Physiopathologie des Syndromes Rares Héréditaires, AVENIR-Inserm, EA3949, Faculté de Médecine de Strasbourg, Université Louis Pasteur, 11 rue Humann, 67085 Strasbourg, France. vincent.marion@medecine.u-strasbg.fr

Abstract

Bardet-Biedl syndrome (BBS) is an inherited ciliopathy generally associated with severe obesity, but the underlying mechanism remains hypothetical and is generally proposed to be of neuroendocrine origin. In this study, we show that while the proliferating preadipocytes or mature adipocytes are nonciliated in culture, a typical primary cilium is present in differentiating preadipocytes. This transient cilium carries receptors for Wnt and Hedgehog pathways, linking this organelle to previously described regulatory pathways of adipogenesis. We also show that the BBS10 and BBS12 proteins are located within the basal body of this primary cilium and inhibition of their expression impairs ciliogenesis, activates the glycogen synthase kinase 3 pathway, and induces peroxisome proliferator-activated receptor nuclear accumulation, hence favoring adipogenesis. Moreover, adipocytes derived from BBS-patients' dermal fibroblasts in culture exhibit higher propensity for fat accumulation when compared to controls. This strongly suggests that a peripheral primary dysfunction of adipogenesis participates to the pathogenesis of obesity in BBS.

PMID:
19190184
PMCID:
PMC2635307
DOI:
10.1073/pnas.0812518106
[Indexed for MEDLINE]
Free PMC Article
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