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Diabetologia. 2017 Jan;60(1):24-29. Epub 2016 Oct 7.

Endotrophin, a multifaceted player in metabolic dysregulation and cancer progression, is a predictive biomarker for the response to PPARγ agonist treatment.

Sun K1,2, Park J1,3, Kim M1,4,5, Scherer PE6,7.

Author information

1
Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390-8549, USA.
2
Center for Metabolic and Degenerative Diseases, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
3
Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, South Korea.
4
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Inje University, Busan, South Korea.
5
Cardiovascular and Metabolic Disease Center, Inje University, Busan, South Korea.
6
Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390-8549, USA. Philipp.Scherer@utsouthwestern.edu.
7
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA. Philipp.Scherer@utsouthwestern.edu.

Abstract

Endotrophin is a cleavage product derived from the collagen VI(α3) chain. Collagen VI is expressed in a number of different tissues, but adipose tissue is a particularly prominent source for this extracellular matrix constituent. Mice lacking collagen VI are metabolically healthier due to reduced fibrosis in adipose tissue. Endotrophin seems to be one of the key players of collagen VI-mediated signalling effects, including its pro-fibrotic nature and chemoattractant properties for macrophages, while also playing an important role in cancer progression and the chemoresistance of tumour cells. The glucose-lowering class of thiazolidinediones (TZDs) that mediate their action through the nuclear receptor peroxisome proliferator-activated receptor (PPAR)γ also exerts important effects on endotrophin by reducing the transcription of parental collagen VI molecules. As with many other pharmacological interventions, there is a range of responses observed in a diabetic patient population. In this issue of Diabetologia, Karsdal and colleagues (DOI: 10.1007/s00125-016-4094-1 ) demonstrate that baseline endotrophin levels offer excellent predictive values to indicate individuals who will show an optimised response to TZDs with respect to the lowering of HbA1c and reduced risk of adverse side effects. The identification of a predictive biomarker for optimal responders is an important step in highlighting the continued viability of TZDs as an effective glucose-lowering class of compounds.

KEYWORDS:

Adverse events; Biomarker; Fibrosis; Non-responders; PPARγ agonist

PMID:
27717959
PMCID:
PMC5136306
DOI:
10.1007/s00125-016-4130-1
[Indexed for MEDLINE]
Free PMC Article

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