Activin A Plays a Critical Role in Proliferation and Differentiation of Human Adipose Progenitors

Abstract

OBJECTIVEGrowth of white adipose tissue takes place in normal development and in obesity. A pool of adipose progenitors is responsible for the formation of new adipocytes and for the potential of this tissue to expand in response to chronic energy overload. However, factors controlling self-renewal of human adipose progenitors are largely unknown. We investigated the expression profile and the role of activin A in this process.RESEARCH DESIGN AND METHODSExpression of INHBA/activin A was investigated in three types of human adipose progenitors. We then analyzed at the molecular level the function of activin A during human adipogenesis. We finally investigated the status of activin A in adipose tissues of lean and obese subjects and analyzed macrophage-induced regulation of its expression.RESULTSINHBA/activin A is expressed by adipose progenitors from various fat depots, and its expression dramatically decreases as progenitors differentiate into adipocytes. Activin A regulates the number of undifferentiated progenitors. Sustained activation or inhibition of the activin A pathway impairs or promotes, respectively, adipocyte differentiation via the C/EBPβ-LAP and Smad2 pathway in an autocrine/paracrine manner. Activin A is expressed at higher levels in adipose tissue of obese patients compared with the expression levels in lean subjects. Indeed, activin A levels in adipose progenitors are dramatically increased by factors secreted by macrophages derived from obese adipose tissue.CONCLUSIONSAltogether, our data show that activin A plays a significant role in human adipogenesis. We propose a model in which macrophages that are located in adipose tissue regulate adipose progenitor self-renewal through activin A.

Adipose Stromal Cells Differentiate Along a Smooth Muscle Lineage Pathway Upon Endothelial Cell Contact via Induction of Activin A

“…Another study has shown that activin A has mitogenic effects on human adipose progenitors and inhibits differentiation along an adipogenic lineage. 38 Although we did not identify significant mitogenic effects of activin A on ASC (data not shown), these findings suggest that activin A plays an important role in promoting a vascular rather than adipogenic lineage fate for ASC, in the region of an endothelial niche.…”

Macrophages Play a Key Role in Angiogenesis and Adipogenesis in a Mouse Tissue Engineering Model

“…Mature adipocytes are not capable of proliferation in vivo, and their regeneration depends on proliferation of adipose progenitor cells. 38,39 A few of the factors controlling the proliferation and differentiation of preadipocytes/progenitor cells are not yet known. FGF-2 has been shown to induce preadipocyte proliferation and inhibit pre-adipocyte differentiation in vitro.…”

Adipogenesis at a glance

“…Multiple signals can influence whether stem cells form adipocytes, including extracellular factors such as the bone morphogenetic proteins (BMPs) (Huang et al, 2009), transforming growth factor  (TGF) (Zamani and Brown, 2010), insulinlike growth factor 1 (IGF1) (Kawai and Rosen, 2010a), interleukin 17 (IL17) (Zúñiga et al, 2010), fibroblast growth factor 1 (FGF1) (Widberg et al, 2009), FGF2 (Xiao et al, 2010) and activin (Zaragosi et al, 2010).…”