{"doi":"10.1016/j.ebiom.2021.103447","title":"Endotrophin: Nominated for best supporting actor in the fibro-inflammatory saga","abstract":"As the population ages, more individuals are at risk of developing age-related chronic diseases, often leading to death. Identifying individuals most at risk for developing multiple co-morbidities could help tailor health care strategies in this growing population. Fibrosis and inflammation are key biological processes involved in the development and progression of a myriad of diseases, including chronic kidney disease, diabetes and cardiovascular diseases. In an article in EBioMedicine [[1]Staunstrup et al. Endotrophin is associated with chronic multimorbidity and all-cause mortality in a cohort of elderly women. https://doi.org/10.1016/j.ebiom.2021.103391Google Scholar], Morten Karsdal and colleagues report the association of circulating levels of a recently described collagen VI cleavage product, referred to as endotrophin, with chronic disease incidence and death in an observational, prospective cohort of elderly Danish women. Participants in this Prospective Epidemiological Risk Factor Study provided fasting blood samples at baseline (n=5,602) and at follow-up (2,094) timepoints. The authors measured the association between serum endotrophin levels and 17 inflammatory and fibro-proliferative chronic diseases that commonly occur in the elderly. Chronic kidney disease demonstrated the strongest association with endotrophin levels, followed by diabetes and cardiovascular diseases. However, it is difficult to know if the elevated serum endotrophin levels in patients with chronic kidney disease are the result of impaired kidney function or a reflection of an actual increase in kidney fibrosis. The authors compared the endotrophin levels with a number of concurrent morbidities. The authors found that the number of chronic diseases increased as endotrophin levels rose, independent of age and BMI. Finally, the authors evaluated the relationship between endotrophin and all-cause mortality up to 1 year after the endotrophin measurements were obtained. They showed that a two-fold increase in endotrophin levels predicted all-cause mortality at baseline (HR = 4.66) and follow-up (HR = 3.53), and they proposed endotrophin as a novel surrogate biomarker for fibroblast activity and progression of chronic disease. As adipose tissues become dysfunctional, the altered physiological state of obese adipose tissue holds the key to enhanced pathologic sequelae across the board [[2]Scherer PE. The Multifaceted Roles of Adipose Tissue-Therapeutic Targets for Diabetes and Beyond: The 2015 Banting Lecture.Diabetes. 2016; 65: 1452-1461Crossref PubMed Scopus (65) Google Scholar]. Adipose tissue that is forced to expand experiences stress at multiple levels. The size of individual adipocytes increases (referred to hypertrophy) prior to the recruitment of additional new adipocytes (referred to as hyperplasia) that help neutralize the excess lipid burden in the system [[3]Sun K Kusminski CM Scherer PE. Adipose tissue remodeling and obesity.J Clin Invest. 2011; 121: 2094-2101Crossref PubMed Scopus (1077) Google Scholar]. Adipose tissue undergoes dramatic changes in the process of expanding its size. One of the key factors as to how well adipocytes handle the expansion process is how successfully the reshaping of the extracellular matrix (ECM) occurs [[4]Sun K Tordjman J Clement K Scherer PE. Fibrosis and adipose tissue dysfunction.Cell Metabolism. 2013; 18: 470-477Summary Full Text Full Text PDF PubMed Scopus (443) Google Scholar]. ECM constituents and the machinery that modifies the ECM plays a critical role in this process. A critical mediator of the ECM in adipose tissue is endotrophin. Endotrophin is the carboxy-terminal cleavage product of the alpha3 chain of collagen VI [[5]Park J Scherer PE. Adipocyte-derived endotrophin promotes malignant tumor progression.J Clin Invest. 2012; 122: 4243-4256Crossref PubMed Scopus (179) Google Scholar]. Collagen VI is ubiquitously expressed, but highly enriched in adipose tissue. Importantly, collagen VI expressio","journal":"EBioMedicine","year":2021,"id":183436,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9617,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":737111,"name":"Olga T. Gupta","orcid":"0000-0003-4808-3100","position":1,"is_corresponding":false},{"id":275031,"name":"Philipp E. Scherer","orcid":"0000-0003-0680-3392","position":0,"is_corresponding":true}],"reference_count":11,"raw_metadata":null,"created_at":"2026-07-18T23:48:22.008011Z","pmid":"34153872","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}