Insulin regulates Bbs4 during adipogenesis.

Bardet-Biedl syndrome (BBS) is a pleiotropic autosomal recessive disorder associated with marked obesity, increased susceptibility to insulin resistance and type 2 diabetes. However, it is unknown whether the link between BBS and diabetes is indirect or direct. Adipogenesis and adipocyte function are regulated by hormonal stimuli, with insulin and insulin growth factor (IGF) playing an important role both in normal and impaired conditions. We have previously shown augmented transcript levels of BBS genes upon induction of adipogenesis. The aim of this study was to investigate the role of insulin in BBS. Through in vitro studies in adipocytes in which Bbs4 expression was either silenced (SiBbs4) or overexpressed (OEBbs4), we showed that insulin and IGF dose- and time-dependently decrease transcription and protein expression of BBS genes during adipogenesis. Silencing of Bbs4 expression in adipocytes significantly impaired and reduced glucose uptake. This effect was reversed by Bbs4 overexpression. Inhibition of PI 3-kinase resulted in upregulation of Bbs transcripts, suggesting that the PI3K pathway is involved in the regulation of these genes. In conclusion, we showed that insulin is a direct regulator of Bbs1, 2, 4 and 6. This hormonal regulation might indicate a metabolic link of these genes to obesity and metabolic syndrome.