Disclosure: The authors have no competing interest. FAH performed experiments, and contributed to discussion and writing of the manuscript, MMM performed experiments and contributed to discussion, MC designed the in vivo experiments and contributed to discussion, YE performed experiments, PK and RG contributed to discussion and reviewed/edited the manuscript, MP designed the study, performed experiments and contributed to discussion, writing and editing of the manuscript.
Histone demethylase KDM1A represses inflammatory gene expression in preadipocytes
Article first published online: 5 JUL 2013
Copyright © 2013 The Obesity Society
Volume 21, Issue 12, pages E616–E625, December 2013
How to Cite
Hanzu, F. A., Musri, M. M., Sánchez-Herrero, A., Claret, M., Esteban, Y., Kaliman, P., Gomis, R. and Párrizas, M. (2013), Histone demethylase KDM1A represses inflammatory gene expression in preadipocytes. Obesity, 21: E616–E625. doi: 10.1002/oby.20479
Funding agencies: This work was supported by grants EFSD/Novo Nordisk awarded to MP, BFU2009-09988/BMC, SAF2010-15050 and SAF2006-07382 from the Spanish Ministry of Science and Innovation (MICINN) awarded to MP, PK and RG respectively. FAH is a recipient of a Rio-Hortega contract from the Instituto de Salud Carlos III (ISCIII, Spain). MMM is a recipient of a Sara Borrell contract from the ISCIII (CD08/00182). MC is a recipient of a Miguel Servet contract (CP09/00233) from the ISCIII.
- Issue published online: 3 DEC 2013
- Article first published online: 5 JUL 2013
- Accepted manuscript online: 17 APR 2013 01:05PM EST
- Manuscript Accepted: 20 MAR 2013
- Manuscript Revised: 19 MAR 2013
- Manuscript Received: 30 NOV 2012
Persistent inflammation and impaired adipogenesis are frequent features of obesity and underlie the development of its complications. However, the factors behind adipose tissue dysfunction are not completely understood. Previously it was shown that histone demethylase KDM1A is required for adipogenesis.
Design and Methods
Kdm1a expression was knocked down in 3T3-L1 preadipocytes by siRNA transfection and whole-genome expression profiling was performed by microarray hybridization. The role of NF-κβ and C/EBPβ was analyzed by incubation with the inhibitor parthenolide and by cebpb knockdown, respectively.
Knockdown of kdm1a or rcor2 in 3T3-L1 preadipocytes results in impaired differentiation and induction of inflammatory gene expression. Enhanced expression of il6 in kdm1a knocked down preadipocytes is associated with increased recruitment of C/EBPβ and the NF-κβ subunit RelA to the il6 promoter. Cebpb knockdown attenuates the induction of il6 expression in kdm1a knocked down cells, whereas simultaneous cebpb knockdown and NF-κβ inhibition abrogates it. Dietary-induced and genetic mouse models of obesity display decreased KDM1A in adipose tissue, and this correlates with increased expression of proinflammatory genes and C/EBPβ.
KDM1A represses the expression of inflammatory genes in preadipocytes. Dysregulated kdm1a expression in preadipocytes may thus participate in the development of obesity-associated inflammation.