High glucose induces adipogenic differentiation of muscle-derived stem cells

被引:223
作者
Aguiari, Paola [2 ]
Leo, Sara [2 ]
Zavan, Barbara [3 ]
Vindigni, Vincenzo [4 ]
Rimessi, Alessandro [2 ]
Bianchi, Katiuscia [2 ]
Franzin, Chiara [5 ]
Cortivo, Roberta [3 ]
Rossato, Marco [5 ]
Vettor, Roberto [5 ]
Abatangelo, Giovanni [3 ]
Pozzan, Tullio [1 ]
Pinton, Paolo [2 ]
Rizzuto, Rosario [2 ]
机构
[1] Univ Padua, CNR, Inst Neurosci, Venetian Inst Mol Med,Dept Biomed Sci, I-35122 Padua, Italy
[2] Univ Ferrara, Interdisciplinary Ctr Study Inflammat, Dept Expt & Diagnost Med, I-44100 Ferrara, Italy
[3] Univ Padua, Dept Histol Microbiol & Med Biotechnol, I-35122 Padua, Italy
[4] Univ Padua, I-35122 Padua, Italy
[5] Univ Padua, Dept Med & Surg Sci, Endocrine Metab Lab, I-35122 Padua, Italy
关键词
adipocyte; hyperglycemia; PKC; ROS;
D O I
10.1073/pnas.0711402105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 PKC beta activation. These two events appear crucial steps in this differentiation process that can be directly induced by oxidizing agents and inhibited by PKC beta siRNA silencing. The differentiated adipocytes, when implanted in vivo, form viable and vascularized adipose tissue. Overall, the data highlight a previously un-characterized 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.
引用
收藏
页码:1226 / 1231
页数:6
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