Integrative genomics reveal a role for MCPIP1 in adipogenesis and adipocyte metabolism
- PDF / 8,082,011 Bytes
- 21 Pages / 595.276 x 790.866 pts Page_size
- 34 Downloads / 171 Views
Cellular and Molecular Life Sciences
ORIGINAL ARTICLE
Integrative genomics reveal a role for MCPIP1 in adipogenesis and adipocyte metabolism Magdalena Losko1 · Dobrochna Dolicka1 · Natalia Pydyn1 · Urszula Jankowska2 · Sylwia Kedracka‑Krok3 · Maria Kulecka4 · Agnieszka Paziewska4 · Michal Mikula5 · Piotr Major6 · Marek Winiarski6 · Andrzej Budzynski6 · Jolanta Jura1 Received: 26 February 2019 / Revised: 23 November 2019 / Accepted: 18 December 2019 © The Author(s) 2019
Abstract Obesity is considered a serious chronic disease, associated with an increased risk of developing cardiovascular diseases, non-alcoholic fatty liver disease and type 2 diabetes. Monocyte chemoattractant protein-1-induced protein-1 (MCPIP1) is an RNase decreasing stability of transcripts coding for inflammation-related proteins. In addition, MCPIP1 plays an important role in the regulation of adipogenesis in vitro by reducing the expression of key transcription factors, including C/EBPβ. To elucidate the role of MCPIP1 in adipocyte biology, we performed RNA-Seq and proteome analysis in 3T3-L1 adipocytes overexpressing wild-type (WTMCPIP1) and the mutant form of MCPIP1 protein (D141NMCPIP1). Our RNA-Seq analysis followed by confirmatory Q-RT-PCR revealed that elevated MCPIP1 levels in 3T3-L1 adipocytes upregulated transcripts encoding proteins involved in signal transmission and cellular remodeling and downregulated transcripts of factors involved in metabolism. These data are consistent with our proteomic analysis, which showed that MCPIP1 expressing adipocytes exhibit upregulation of proteins involved in cellular organization and movement and decreased levels of proteins involved in lipid and carbohydrate metabolism. Moreover, MCPIP1 adipocytes are characterized by decreased level of insulin receptor, reduced insulin-induced Akt phosphorylation, as well as depleted Glut4 level and impaired glucose uptake. Overexpression of Glut4 in 3T3-L1 cells expressed WTMCPIP1 rescued adipogenesis. Interestingly, we found decreased level of MCPIP1 along with an increase in body mass index in subcutaneous adipose tissue. The presented data show a novel role of MCPIP1 in modulating insulin sensitivity in adipocytes. Overall, our findings demonstrate that MCPIP1 is an important regulator of adipogenesis and adipocyte metabolism. Keywords Regnase-1 · Pparγ · C/EBPα · Lipid homeostasis
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00018-019-03434-5) contains supplementary material, which is available to authorized users. * Jolanta Jura [email protected] 1
Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30‑387 Kraków, Poland
2
Proteomics and Mass Spectrometry Laboratory, Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7A, 30‑387 Kraków, Poland
3
Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30
Data Loading...
