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High glucose induces adipogenic differentiation of muscle-derived stem cells
Paolo Pinton*, and
*Department of Experimental and Diagnostic Medicine, Interdisciplinary Center for the Study of Inflammation, University of Ferrara, 44100 Ferrara, Italy; Department of Histology, Microbiology and Medical Biotechnologies, University of Padua, 35122 Padua, Italy; Clinic of Plastic Surgery, University of Padua, 35122 Padua, Italy; Endocrine-Metabolic Laboratory, Internal Medicine, Department of Medical and Surgical Sciences, University of Padua, 35122 Padua, Italy; and ¶Department of Biomedical Sciences, CNR Institute of Neuroscience, and Venetian Institute of Molecular Medicine, University of Padua, 35122 Padua, Italy
Contributed by Tullio Pozzan, December 5, 2007
Received for publication September 14, 2007.
Regeneration of mesenchymal tissues depends on a resident stemcell population, that in most cases remains elusive in termsof cellular identity and differentiation signals. We here showthat primary cell cultures derived from adipose tissue or skeletalmuscle differentiate into adipocytes when cultured in high glucose.High glucose induces ROS production and PKCβ activation.These two events appear crucial steps in this differentiationprocess that can be directly induced by oxidizing agents andinhibited by PKCβ siRNA silencing. The differentiated adipocytes,when implanted in vivo, form viable and vascularized adiposetissue. Overall, the data highlight a previously uncharacterizeddifferentiation route triggered by high glucose that drivesnot only resident stem cells of the adipose tissue but alsouncommitted precursors present in muscle cells to form adiposedepots. This process may represent a feed-forward cycle betweenthe regional increase in adiposity and insulin resistance thatplays a key role in the pathogenesis of diabetes mellitus.
Key Words: adipocyte hyperglycemia PKC ROS
Author contributions: P.A., S.L., and B.Z. contributed equallyto this work; P.P. and R.R. designed research; P.A., S.L., B.Z.,V.V., A.R., K.B., and C.F. performed research; P.A., S.L., B.Z.,A.R., R.C., M.R., R.V., G.A., T.P., and P.P. analyzed data;and R.R. wrote the paper.