HOX gene network is involved in the transcriptional regulation of in vivo human adipogenesis

Adipogenesis is regulated by the sequential activation of a series of transcription factors: the C/EBP proteins of type beta and delta trigger the process while PPARgamma and C/EBPalpha induce the differentiation from pre-adipocyte to adipocyte, followed by adipo-specific gene expression. A number of observations suggest the involvement of genes controlling embryonal development in adipogenesis. In human thyroid follicular carcinoma, it has been recently identified an oncogenetic fusion protein resulting from the interaction between the isoform PPARgamma1 of PPARgamma and the homeoprotein encoded by the PAX-8 gene. Recent observations have pointed out that gene expression associated with adipocyte differentiation in vivo and in vitro, although partially overlapping, is actually different. HOX genes make up a network of transcription factors (homeoproteins) controlling embryonal development as well as crucial functions of adult eukaryotic cells. The molecular organization of this network of 39 genes appears to be unique in the genome and probably acts regulating phenotypic cell identity. In the present study we have analyzed the expression of the complete HOX gene network, in vivo, in different deposits of human white adipose tissue and in embryonal brown adipose tissues. Most of the genes in the HOX network are active in white as well as brown adipose tissue. Furthermore HOX genes display a deposit-specific expression in white adipose tissue. Moreover, expression of the paralogous group 4 genes (HOX A4, HOX B4, HOX C4, and HOX D4), together with that of isolated genes in the network, appears to discriminate between white and brown adipose tissue. This data allows us to postulate the involvement of the HOX network in transcriptional regulation of human adipogenesis and to hypothesize on the molecular mechanisms that could be implicated. (C) 2002 Wiley-Liss, Inc.