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

TY - JOUR

T1 - Depletion of Jmjd1c impairs adipogenesis in murine 3T3-L1 cells

AU - Buerger, Florian

AU - Müller, Silvana

AU - Ney, Nadja

AU - Weiner, Juliane

AU - Heiker, John T

AU - Kallendrusch, Sonja

AU - Kovacs, Peter

AU - Schleinitz, Dorit

AU - Thiery, Joachim

AU - Stadler, Sonja C

AU - Burkhardt, Ralph

N1 - Copyright © 2017 Elsevier B.V. All rights reserved.

PY - 2017/7

Y1 - 2017/7

N2 - 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.

AB - 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.

KW - 3T3-L1 Cells

KW - Adipocytes/cytology

KW - Adipogenesis

KW - Animals

KW - CCAAT-Enhancer-Binding Proteins/genetics

KW - Cell Differentiation

KW - Fatty Acids/genetics

KW - Fibroblasts/cytology

KW - Glucose/genetics

KW - Histones/genetics

KW - Jumonji Domain-Containing Histone Demethylases/deficiency

KW - Lipid Droplets/metabolism

KW - Mice

KW - Mitosis

KW - PPAR gamma/genetics

KW - Promoter Regions, Genetic

U2 - 10.1016/j.bbadis.2017.05.011

DO - 10.1016/j.bbadis.2017.05.011

M3 - SCORING: Journal article

C2 - 28501567

VL - 1863

SP - 1709

EP - 1717

JO - BBA-MOL BASIS DIS

JF - BBA-MOL BASIS DIS

SN - 0925-4439

IS - 7

ER -