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

作者：Zaragosi Laure Emmanuelle; Wdziekonski Brigitte; Villageois Phi; Keophiphath Mayoura; Maumus Marie; Tchkonia Tamara; Bourlier Virginie; Mohsen Kanson Tala; Ladoux Annie; Elabd Christian; Scheideler Marcel; Trajanoski Zlatko; Takashima Yasuhiro; Amri Ez Zoubir; Lacasa Daniele; Sengenes Coralie; Ailhaud Gerard; Clement Karine; Bouloumie Anne; Kirkland James L; Dani Christian^*

来源：Diabetes, 2010, 59(10): 2513-2521.

DOI：10.2337/db10-0013

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/EBP beta-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 self-renewal through activin A. Diabetes 59: 2513-2521, 2010

• 出版日期2010-10