Activin a plays a critical role in proliferation and differentiation of human adipose progenitors.
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.


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.
Zaragosi
Laure-Emmanuelle
LE
UMR6543 Centre National de la Recherche Scientifique, Institute of Developmental Biology and Cancer, University of Nice Sophia-Antipolis, Nice, France.
Wdziekonski
Brigitte
B
Villageois
Phi
P
Keophiphath
Mayoura
M
Maumus
Marie
M
Tchkonia
Tamara
T
Bourlier
Virginie
V
Mohsen-Kanson
Tala
T
Ladoux
Annie
A
Elabd
Christian
C
Scheideler
Marcel
M
Trajanoski
Zlatko
Z
Takashima
Yasuhiro
Y
Amri
Ez-Zoubir
EZ
Lacasa
Daniele
D
Sengenes
Coralie
C
Ailhaud
Gérard
G
Clément
Karine
K
Bouloumie
Anne
A
Kirkland
James L
JL
Dani
Christian
C
D028341:Activins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D000328:Adult; D002454:Cell Differentiation; D002455:Cell Division; D012321:DNA-Directed RNA Polymerases / Q000187:drug effects / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation; D005954:Glucosephosphate Dehydrogenase / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009767:Obesity, Morbid / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D035181:TATA-Box Binding Protein / Q000187:drug effects / Q000235:genetics; D013851:Thinness / Q000473:pathology*
D035181:TATA-Box Binding Protein; C509817:TBP protein, human; C422405:activin A; D028341:Activins; D003907:Dexamethasone; D005954:Glucosephosphate Dehydrogenase; D012321:DNA-Directed RNA Polymerases