High glucose induces adipogenic differentiation of muscle-derived stem cells.
Regeneration of mesenchymal tissues depends on a resident stem cell population, that in most cases remains elusive in terms of cellular identity and differentiation signals. We here show that primary cell cultures derived from adipose tissue or skeletal muscle differentiate into adipocytes when cultured in high glucose. High glucose induces ROS production and PKCbeta activation. These two events appear crucial steps in this differentiation process that can be directly induced by oxidizing agents and inhibited by PKCbeta siRNA silencing. The differentiated adipocytes, when implanted in vivo, form viable and vascularized adipose tissue. Overall, the data highlight a previously uncharacterized differentiation route triggered by high glucose that drives not only resident stem cells of the adipose tissue but also uncommitted precursors present in muscle cells to form adipose depots. This process may represent a feed-forward cycle between the regional increase in adiposity and insulin resistance that plays a key role in the pathogenesis of diabetes mellitus.
Aguiari
Paola
P
Department of Experimental and Diagnostic Medicine, Interdisciplinary Center for the Study of Inflammation, University of Ferrara, 44100 Ferrara, Italy.
Leo
Sara
S
Zavan
Barbara
B
Vindigni
Vincenzo
V
Rimessi
Alessandro
A
Bianchi
Katiuscia
K
Franzin
Chiara
C
Cortivo
Roberta
R
Rossato
Marco
M
Vettor
Roberto
R
Abatangelo
Giovanni
G
Pozzan
Tullio
T
Pinton
Paolo
P
Rizzuto
Rosario
R
D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism* / Q000637:transplantation / Q000648:ultrastructure; D050156:Adipogenesis / Q000187:drug effects* / Q000502:physiology; D000273:Adipose Tissue / Q000098:blood supply / Q000166:cytology / Q000648:ultrastructure; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D011923:Rats, Nude; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure
D015415:Biomarkers; D017077:Culture Media, Conditioned; D005947:Glucose