Role of preadipocyte factor I in adipocyte differentiation

Preadipocyte factor 1 (Pref-I) is an EGF-repeat-containing transmembrane protein that inhibits adipogenesis. The extracellular domain of Pref-I is cleaved by TNF-alpha converting enzyme to generate the biologically active soluble form of Pref-I. The role of Pref-I in adipogenesis has been firmly established by in vitro and in vivo studies. Pref-I activates ERK/MAPK and upregulates Sox9 expression to inhibit adipocyte differentiation. Sox9 directly binds to the promoter regions of CCAAT/enhancer-binding protein-beta and CCAAT/enhancer-binding protein-delta in order to suppress their promoter activities in preventing adipocyte differentiation. Here, we describe the function of Pref-I in adipocyte differentiation and the recent findings on the mechanisms by which Pref-I inhibits adipocyte differentiation.