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Biochim Biophys Acta Mol Basis Dis. 2017 Jul;1863(7):1709-1717. doi: 10.1016/j.bbadis.2017.05.011. Epub 2017 May 10.

Depletion of Jmjd1c impairs adipogenesis in murine 3T3-L1 cells.

Author information

1
Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, 04103 Leipzig, Germany; LIFE-Leipzig Research Center for Civilization Diseases, University of Leipzig, 04103 Leipzig, Germany.
2
Leipzig University Medical Center, Integrated Research and Treatment Centre Adiposity Diseases, University of Leipzig, 04103 Leipzig, Germany.
3
Institute of Anatomy, University of Leipzig, 04103 Leipzig, Germany.
4
Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, 04103 Leipzig, Germany; LIFE-Leipzig Research Center for Civilization Diseases, University of Leipzig, 04103 Leipzig, Germany. Electronic address: ralph.burkhardt@medizin.uni-leipzig.de.

Abstract

Differentiation of adipocytes is a highly regulated process modulated by multiple transcriptional co-activators and co-repressors. JMJD1C belongs to the family of jumonji C (jmjC) domain-containing histone demethylases and was originally described as a ligand-dependent co-activator of thyroid hormone and androgen receptors. Here, we explored the potential role of Jmjd1c in white adipocyte differentiation. To investigate the relevance of Jmjd1c in adipogenesis, murine 3T3-L1 preadipocyte cells with transient knock-down of Jmjd1c (3T3_Jmjd1c) were generated. Depletion of Jmjd1c led to the formation of smaller lipid droplets, reduced accumulation of triglycerides and maintenance of a more fibroblast-like morphology after adipocyte differentiation. Concomitantly, insulin stimulated uptake of glucose and fatty acids was significantly reduced in 3T3_Jmjd1c adipocytes. In line with these observations we detected lower expression of key genes associated with lipid droplet formation (Plin1, Plin4, Cidea) and uptake of glucose and fatty acids (Glut4, Fatp1, Fatp4, Aqp7) respectively. Finally, we demonstrate that depletion of Jmjd1c interferes with mitotic clonal expansion (MCE), increases levels of H3K9me2 (dimethylation of lysine 9 of histone H3) at promotor regions of adipogenic transcription factors (C/EBPs and PPARγ) and leads to reduced induction of these key regulators. In conclusion, we have identified Jmjd1c as a modulator of adipogenesis. Our data suggest that Jmjd1c may participate in MCE and the activation of the adipogenic transcription program during the induction phase of adipocyte differentiation in 3T3-L1 cells.

KEYWORDS:

Adipogenesis; H3K9me2; Histone modification; Mitotic clonal expansion; WAT; jumonji

PMID:
28501567
DOI:
10.1016/j.bbadis.2017.05.011
[Indexed for MEDLINE]
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