PMID:19190184

Citation	Marion, V, Stoetzel, C, Schlicht, D, Messaddeq, N, Koch, M, Flori, E, Danse, JM, Mandel, JL and Dollfus, H (2009) Transient ciliogenesis involving Bardet-Biedl syndrome proteins is a fundamental characteristic of adipogenic differentiation. Proc. Natl. Acad. Sci. U.S.A. 106:1820-5
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.
Links	PubMed PMC2635307 Online version:10.1073/pnas.0812518106
Keywords	Adipocytes/cytology; Adipogenesis; Bardet-Biedl Syndrome/pathology; Bardet-Biedl Syndrome/physiopathology; Cell Differentiation; Cells, Cultured; Chaperonins/physiology; Cilia/pathology; Group II Chaperonins; Humans; Morphogenesis; Obesity/etiology; Signal Transduction
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:BBS10		GO:0042384: cilium assembly	ECO:0000315:		P		Fig 4. Cilium formation inhibited upon BBS10 knockdown, given localisation and predicted chaperonine function they assist the formation of ciliary components not directly involved in intragellar transport.	complete
HUMAN:BBS10		GO:0005814: centriole	ECO:0000270:		C		Fig 1B. human adipocyte cells with immunolabelled labelled centrioles and immunodetection of BBS10 showed localisation to the centrioles.	complete
HUMAN:BBS10		GO:0005932: microtubule basal body	ECO:0000314:		C		Fig 1. human primary renal proximal tubular epithelial cells with immunolabelled labelled cilium showed the basal body, and immunodetection of BBS10 showed localisation to the basal body of the primary cilium.	complete
HUMAN:BBS10		GO:0035356: cellular triglyceride homeostasis	ECO:0000315:		P		Fig. 6C: Fluorescent staining showed increased triglyceride accumulation in BBS patient cultured fibroblasts.	complete
HUMAN:BBS12		GO:0042384: cilium assembly	ECO:0000315:		P		Fig 4. Cilium formation inhibited upon BBS12 knockdown, given localisation and predicted chaperonine function they assist the formation of ciliary components not directly involved in intragellar transport.	complete
HUMAN:BBS12		GO:0005932: microtubule basal body	ECO:0000314:		C		Fig 1A. human primary renal proximal tubular epithelial cells with immunolabelled cilium showed BBS12 was localised to the basal body of the primary cilium	complete
HUMAN:BBS12		GO:0035356: cellular triglyceride homeostasis	ECO:0000315:		P		Fig. 6C: Increased intracellular triglyceride accumulation in cultured adipocytes of BBS patient fibroblasts stained with Adipored Assay Reagent.	complete

References

See Help:References for how to manage references in GONUTS.