Loss of the tumor suppressor gene AIP mediates the browning of human brown fat tumors

Human brown fat tumors (hibernomas) display concomitant loss of the tumor suppressor genes MEN1 and AIP. In the present study, we hypothesized that the brown fat phenotype is attributed to these mutations. Accordingly, we demonstrate that silencing of AIP in human brown preadipocytic and white fat cell lines results in the induction of the brown fat marker UCP1. In human adipocytic tumors, loss of MEN1 was found both in white (one out of 51 lipomas) and brown fat tumors. In contrast, concurrent loss of AIP was always accompanied by a brown fat morphology. We conclude that this white-to-brown phenotype switch in brown fat tumors is mediated by the loss of AIP. Array-based global gene expression analysis of hibernoma (n=14), white benign (n=49) and malignant (n=23) adipocytic tumors. RNA was extracted from frozen tumor biopsies and hybridized onto Affymetrix Human Gene 1.0 ST arrays.