Identification of a Paracrine Signaling Mechanism Linking CD34high Progenitors to the Regulation of Visceral Fat Expansion and Remodeling

Abstract

Summary: Accumulation of visceral (VIS) is a predictor of metabolic disorders and insulin resistance. This is due in part to the limited capacity of VIS fat to buffer lipids allowing them to deposit in insulin-sensitive tissues. Mechanisms underlying selective hypertrophic growth and tissue remodeling properties of VIS fat are not well understood. We identified subsets of adipose progenitors (APs) unique to VIS fat with differential Cd34 expression and adipogenic capacity. VIS low (Cd34 low) APs are adipogenic, whereas VIS high (Cd34 high) APs are not. Furthermore, VIS high APs inhibit adipogenic differentiation of SUB and VIS low APs in vitro through the secretion of soluble inhibitory factor(s). The number of VIS high APs increased with adipose tissue expansion, and their abundance in vivo caused hypertrophic growth, fibrosis, inflammation, and metabolic dysfunction. This study unveils the presence of APs unique to VIS fat involved in the paracrine regulation of adipogenesis and tissue remodeling. : Buffolo et al. show that the visceral fat of mice contains subsets of Cd34 positive stromal cells with distinct adipogenic potential. Stromal cells with high Cd34 expression inhibit adipogenic conversion of cells with low Cd34 expression. When implanted in vivo, Cd34 high stromal cells cause visceral adipose tissue remodeling and inflammation and impair insulin sensitivity. Keywords: adipose progenitors, fat expansion, cell sorting, transplantation, visceral fat