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

Kai Sun, Jiyoung Park, Min Kim, Philipp E. Scherer

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.