Identification of brown adipocyte progenitors

Abstract

Today’s therapy against obesity uses life style changing and/or medication, but is little promising so far. Therefore it is important to develop new and successful therapeutically strategies against obesity. Nowadays brown adipose tissue gives hope to develop new therapeutically strategies and therapies against obesity because of its energy combusting function. It has been shown from different workgroups that brown adipose tissue (BAT) with uncoupling protein 1 (UCP1) plays an important role in the regulation of body weight. Because of the therapeutically potential of BAT it is important to know where brown adipocytes in adults derive from. The nature of BAT found in human adults is currently under debate. The aim of this study was to further characterise brown adipose tissue in human adults, therefore novel markers of human brown adipocyte progenitors were identified and these were compared with white adipose tissue progenitors. Thus, progenitor cells from paired samples of deep neck (dn) and subcutaneous (sc) neck adipose tissue were isolated and gene expression patterns were analysed using gene array analysis. It was hypothesised that brown adipocytes in human adults derive from a specific subset of progenitors that differs from white preadipocytes. Human primary cells were chosen for investigation. Tissue samples were obtained from 52 patients. Interestingly, progenitor cells isolated from dn adipose tissue showed higher expression of UCP1 than cells isolated from sc adipose tissue suggesting two different progenitor cell pools. 92 genes were differentially regulated in progenitor cells from dn adipose tissue versus sc adipose tissue, among them fibroblast growth factor 16 (FGF16), bone morphogenetic protein 4 (BMP4), cluster of differentiation 34 (CD34), alcohol dehydrogenase 1B (ADH1B) and odd-oz/ten-m homolog 2 (ODZ2). Small interfering ribonucleic acid (siRNA)-mediated downregulation of ODZ2 in Simpson-Golabi-Behmel-Syndrome (SGBS) peradipocytes resulted in an upregulation of UCP1 suggesting a role of ODZ2 in brown adipogenesis.