Transient ciliogenesis involving Bardet-Biedl syndrome proteins is a fundamental characteristic of adipogenic differentiation.
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.
Marion
Vincent
V
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
Stoetzel
Corinne
C
Schlicht
Dominique
D
Messaddeq
Nadia
N
Koch
Michael
M
Flori
Elisabeth
E
Danse
Jean Marc
JM
Mandel
Jean-Louis
JL
Dollfus
Hélène
H
D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis; D020788:Bardet-Biedl Syndrome / Q000473:pathology* / Q000503:physiopathology; D002454:Cell Differentiation; D002478:Cells, Cultured; D018833:Chaperonins / Q000502:physiology*; D002923:Cilia / Q000473:pathology*; D056385:Group II Chaperonins; D006801:Humans; D009024:Morphogenesis; D009765:Obesity / Q000209:etiology; D015398:Signal Transduction
C512111:BBS10 protein, human; C517002:BBS12 protein, human; D018833:Chaperonins; D056385:Group II Chaperonins