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 and Philipp E. Scherer ()
Additional contact information
Kai Sun: Touchstone Diabetes Center, University of Texas Southwestern Medical Center
Jiyoung Park: Touchstone Diabetes Center, University of Texas Southwestern Medical Center
Olga T. Gupta: Touchstone Diabetes Center, University of Texas Southwestern Medical Center
William L. Holland: Touchstone Diabetes Center, University of Texas Southwestern Medical Center
Pernille Auerbach: University of Copenhagen
Ningyan Zhang: Brown Foundation Institute of Molecular Medicine, Texas Therapeutics Institute, University of Texas Health Science Center at Houston
Roberta Goncalves Marangoni: Northwestern University, Feinberg School of Medicine
Sarah M. Nicoloro: Program in Molecular Medicine, University of Massachusetts Medical School
Michael P. Czech: Program in Molecular Medicine, University of Massachusetts Medical School
John Varga: Northwestern University, Feinberg School of Medicine
Thorkil Ploug: University of Copenhagen
Zhiqiang An: Brown Foundation Institute of Molecular Medicine, Texas Therapeutics Institute, University of Texas Health Science Center at Houston
Philipp E. Scherer: Touchstone Diabetes Center, University of Texas Southwestern Medical Center

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: 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.

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4485

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DOI: 10.1038/ncomms4485

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