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OBJECTIVE--Growth 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 METHODS--Expression 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. RESULTS--INHBA/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. CONCLUSIONS--Altogether, 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 serf-renewal through activin A. Diabetes 59: 2513-2521, 2010, Growth of white adipose tissue in normal development and in obesity is the result of an increase in size and number of adipocytes. Given that mature adipocytes do not divide [...]

Lipoprotein particles containing apoA-1 but not apoA-ll are, among high-density lipoproteins, effective protectors against atherosclerosis that act by promoting the efflux of cellular cholesterol and the reverse cholesterol transport process. [...]

Ptprv is a transmembrane tyrosine phosphatase expressed in embryonic stem cells, gonads, and osteoblast precursors. In bone formation, it has been characterized as a molecular marker of mesenchymal bone collar cells and shown to play a role in osteoblast differentiation. We show for the first time that Ptprv is also expressed in adipose tissue. In this tissue, Ptprv expression is restricted to cells of the stroma vascular fraction, which contain adipocyte precursors, but is not detected in differentiated adipocytes. Moreover, Ptprv expression is regulated. Indeed, both in 3T3L1 cells and mouse embryo fibroblast models of adipocyte differentiation, Ptprv expression increases when cells reach confluence and then decreases upon exposure to adipogenic conditions. However, Ptprv expression patterns do not strictly overlap with Pref-1 and ACLP, two proteins expressed in preadipocytes but not in adipocytes. In addition, Ptprv does not appear as a critical player in adipocyte differentiation, since MEF cells lacking Ptprv are able to differentiate into adipocytes and mice lacking Ptprv have normal adipose tissue development. It is thus likely that this phosphatase does not play an important role in adipose tissue biology. Moreover, we have cloned the human ortholog of Ptprv and shown that this gene 1) has no 'functional' parent in the human genome, 2) has retained an 'intron-exon' structure, and 3) is transcribed in a regulated manner. Taken together, these results indicate that Ptprv is the only PTP-ase whose function has been lost during the evolution process between rodents and humans., From the CNRS UMR 6543 Institute of Signaling Developmental Biology and Cancer, Faculte des Sciences, Pare Valrose, Nice, France. Address correspondence to Pascal Peraldi. E-mail: [...]