Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • 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
  • Ploug, Thorkil
  • Zhiqiang An
  • Philipp E Scherer

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.

TidsskriftNature Communications
Antal sider1
StatusUdgivet - mar. 2014

ID: 113981355