Spontaneously beating cardiomyocytes derived from white mature adipocytes.
OBJECTIVE
Adipose stromal cells and dissociated brown adipose tissue have been shown to generate cardiomyocyte-like cells. However, it is not clear whether white mature adipocytes have the same potential, even though a close relationship has been found between adipocytes and vascular endothelial cells, another cardiovascular cell type. The objective of this study was to examine if white adipocytes would be able to supply cardiomyocytes.


RESULTS
We prepared a highly purified population of lipid-filled adipocytes from mice, 6-7 weeks of age. When allowed to lose lipids, the adipocytes assumed a fibroblast-like morphology, so-called dedifferentiated fat (DFAT) cells. Subsequently, 10-15% of the DFAT cells spontaneously differentiated into cardiomyocyte-like cells, in which the cardiomyocyte phenotype was identified by morphological observations, expression of cardiomyocyte-specific markers, and immunocytochemical staining. In addition, electrophysiological studies revealed pacemaker activity in these cells, and functional studies showed that a beta-adrenergic agonist stimulated the beating rate, whereas a beta-antagonist reduced it. In vitro treatment of newly isolated adipocytes or DFAT cells with inhibitors of bone morphogenetic proteins (BMP) and Wnt signalling promoted the development of the cardiomyocyte phenotype as determined by the number or beating colonies of cardiomyocyte-like cells and expression of troponin I, a cardiomyocyte-specific marker. Inhibition of BMP was most effective in promoting the cardiomyocyte phenotype in adipocytes, whereas Wnt-inhibition was most effective in DFAT cells.


CONCLUSIONS
White mature adipocytes can differentiate into cardiomyocyte-like cells, suggesting a link between adipocyte and cardiomyocyte differentiation.
Jumabay
Medet
M
David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, USA.
Zhang
Rui
R
Yao
Yucheng
Y
Goldhaber
Joshua I
JI
Boström
Kristina I
KI
D000200:Action Potentials; D052438:Adipocytes, White / Q000166:cytology*; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D050991:GATA4 Transcription Factor / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000166:cytology*; D010641:Phenotype; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000502:physiology
D019485:Bone Morphogenetic Proteins; D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D051153:Wnt Proteins; D002118:Calcium