Format

Send to

Choose Destination
Stem Cell Reports. 2017 May 9;8(5):1164-1173. doi: 10.1016/j.stemcr.2017.03.014. Epub 2017 Apr 13.

Activation of IRF1 in Human Adipocytes Leads to Phenotypes Associated with Metabolic Disease.

Author information

1
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Department of Anatomy and Embryology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
2
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
3
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
4
Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
5
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Nephrology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
6
Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94143, USA; California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA; Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94143, USA.
7
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. Electronic address: chadacowan@gmail.com.

Abstract

The striking rise of obesity-related metabolic disorders has focused attention on adipocytes as critical mediators of disease phenotypes. To better understand the role played by excess adipose in metabolic dysfunction it is crucial to decipher the transcriptional underpinnings of the low-grade adipose inflammation characteristic of diseases such as type 2 diabetes. Through employing a comparative transcriptomics approach, we identified IRF1 as differentially regulated between primary and in vitro-derived genetically matched adipocytes. This suggests a role as a mediator of adipocyte inflammatory phenotypes, similar to its function in other tissues. Utilizing adipose-derived mesenchymal progenitors we subsequently demonstrated that expression of IRF1 in adipocytes indeed contributes to upregulation of inflammatory processes, both in vitro and in vivo. This highlights IRF1's relevance to obesity-related inflammation and the resultant metabolic dysregulation.

KEYWORDS:

IRF1; adipose inflammation; human adipocytes; metabolic disease

PMID:
28416283
PMCID:
PMC5425619
DOI:
10.1016/j.stemcr.2017.03.014
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center