Endotrophin (ETP)

Endotrophin is a bioactive peptide fragment derived from the C-terminal cleavage of the collagen type VI alpha 3 (COL6A3) chain. It functions as a potent adipokine and matrikine, serving as a key mediator in the fibro-inflammatory axis across various tissues, including adipose, heart, kidney, and liver (1.1.2, 1.3.1). Endotrophin exerts its biological effects by promoting tissue fibrosis, chronic inflammation, and angiogenesis, often through the activation of signaling pathways such as the CD44-STAT3 axis (1.1.1, 1.3.2). In the context of metabolic disease, elevated endotrophin levels are strongly associated with obesity-induced insulin resistance and adipose tissue dysfunction (1.2.1, 1.3.5). In oncology, endotrophin acts as a pro-tumorigenic factor that enhances epithelial-mesenchymal transition (EMT), promotes metastasis, and confers resistance to chemotherapeutic agents like cisplatin (1.1.2, 1.2.3). Therapeutic targeting of endotrophin involves the use of neutralizing monoclonal antibodies, small molecule inhibitors of its proteolytic release, or transcriptional suppressors like thiazolidinediones (1.2.1, 1.3.3). As a circulating biomarker, typically measured via the PRO-C6 assay, endotrophin levels are highly prognostic for adverse outcomes in heart failure, chronic kidney disease, and overall mortality (1.4.1, 1.4.3).

Other names

ETPCOL6A3-derived endotrophinCollagen type VI alpha 3 C-terminal fragmentC5 domain of Collagen VI alpha 3

Therapeutic strategies targeting endotrophin include the use of monoclonal antibodies to neutralize the circulating peptide, small molecules like nigericin to inhibit its proteolytic cleavage from the parent COL6A3 chain, and PPAR-gamma agonists to suppress the transcription of the parent collagen molecule (1.1.3, 1.2.1, 1.3.3).