Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction

Kai Sun, Jiyoung Park, Olga T. Gupta, William L. Holland, Pernille Auerbach, Ningyan Zhang, Roberta Goncalves Marangoni, Sarah M. Nicoloro, Michael P. Czech, John Varga, Thorkil Ploug, Zhiqiang An, Philipp E. Scherer

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

Abstract

We recently identified endotrophin as an adipokine with potent tumour-promoting effects. However, the direct effects of local accumulation of endotrophin in adipose tissue have not yet been studied. Here we use a doxycycline-inducible adipocyte-specific endotrophin overexpression model to demonstrate that endotrophin plays a pivotal role in shaping a metabolically unfavourable microenvironment in adipose tissue during consumption of a high-fat diet (HFD). Endotrophin serves as a powerful co-stimulator of pathologically relevant pathways within the 'unhealthy' adipose tissue milieu, triggering fibrosis and inflammation and ultimately leading to enhanced insulin resistance. We further demonstrate that blocking endotrophin with a neutralizing antibody ameliorates metabolically adverse effects and effectively reverses metabolic dysfunction induced during HFD exposure. Collectively, our findings demonstrate that endotrophin exerts a major influence in adipose tissue, eventually resulting in systemic elevation of pro-inflammatory cytokines and insulin resistance, and the results establish endotrophin as a potential target in the context of metabolism and cancer.

Original languageEnglish (US)
Article number3485
Pages (from-to)3485
Number of pages1
JournalNature communications
Volume5
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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