TY - JOUR
T1 - Activin A plays a critical role in proliferation and differentiation of human adipose progenitors
AU - Zaragosi, Laure Emmanuelle
AU - Wdziekonski, Brigitte
AU - Villageois, Phi
AU - Keophiphath, Mayoura
AU - Maumus, Marie
AU - Tchkonia, Tamara
AU - Bourlier, Virginie
AU - Mohsen-Kanson, Tala
AU - Ladoux, Annie
AU - Elabd, Christian
AU - Scheideler, Marcel
AU - Trajanoski, Zlatko
AU - Takashima, Yasuhiro
AU - Amri, Ez Zoubir
AU - Lacasa, Daniele
AU - Sengenes, Coralie
AU - Ailhaud, Gérard
AU - Clément, Karine
AU - Bouloumie, Anne
AU - Kirkland, James L.
AU - Dani, Christian
PY - 2010/10
Y1 - 2010/10
N2 - 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 self-renewal through activin A.
AB - 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 self-renewal through activin A.
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U2 - 10.2337/db10-0013
DO - 10.2337/db10-0013
M3 - Article
C2 - 20530742
AN - SCOPUS:77957589305
SN - 0012-1797
VL - 59
SP - 2513
EP - 2521
JO - Diabetes
JF - Diabetes
IS - 10
ER -