Endocrine Abstracts

Long considered as a vestige of evolution, the primary cilium has recently emerged as a crucial orgnalle in the regulation of cell function. Ciliated cells are ubiquitously present in the organism and until recently only two cellular types were considered as unciliated cells, namely the adipocyte and the hepatocyte. An in vitro approach evidenced that the preadipocyte was transiently ciliated during its terminal differentiation phase and that the primary cilium was acting as a detection siege for anti-adipogenic signals as it carried both the Wnt receptor as well as the Sonic Hedgehog receptor, Smoothened. Inactivation of the chaperone-like BBS protein resulted in unciliated preadiocytes which were more prone to undergo terminal differentiation as well as massive triglyceride accumulation combined with higher leptin secretion; a situation found back when using dermal fibroblasts derived from BBS patients. BBS-associated obesity has been described to be of central origin, namely due to a leptin resistance as the hypothalamic arcuate nuclei were unable to sense plasma leptin. Our data indicate that the BBS-associated obesity could be of two origins, namely from a central hypothalamic dysfuntion and from a more peripheric adipocyte-related one. Further in vivo studies on the adipocytes of our newly generated Bbs12 knock out mice and of the leptin resistant mouse, the Ob/Ob mouse, tend to confirm our previous in vitro findings that BBS-related obesity is not solely linked to a leptin resistant status.