Serum endotrophin levels in patients with heart failure with reduced and mid-range ejection fraction

Eruzun, Hasan; Toprak, İlkim Deniz; Arman, Yücel; Yilmaz, Uğur; Özcan, Mustafa; Kutlu, Yasin; Irmak, Sedat; Kutlu, Orkide; Yoldemir, Şengül Aydin; Altun, Özgür; Çil, Eylem Özgün; Tükek, Tufan

doi:10.1016/j.ejim.2019.04.016

Cited by 8 publications

(4 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Importantly, we recently discovered that the carboxy-terminal C5 domain of the ␣3 chain is proteolytically cleaved from the parental COL6 microfibrils during the secretion process (20,32,33). The product of this cleavage step, named endotrophin, is stable and has been found to be enriched not only in obese adipose tissue but also in the circulation and urine of the patients with certain heart or kidney conditions (34)(35)(36). Moreover, endotrophin is found at higher levels in human breast cancer specimens (20,30).…”

mentioning

confidence: 99%

“…In the tumor tissue, endotrophin increases fibrosis, angiogenesis and is a proinflammatory player via activating transforming growth factor ␤ (TGF-␤) signaling (20). Most recently, a clinical study revealed that circulating endotrophin is correlated with heart failure (34). Two other observations indicate that urinary endotrophin is associated with development of end-stage renal diseases and serum endotrophin levels correlate with increased mortality in chronic kidney disease (35,36).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Critical Role of Matrix Metalloproteinase 14 in Adipose Tissue Remodeling during Obesity

Zhao

Chen

et al. 2020

Molecular and Cellular Biology

View full text Add to dashboard Cite

Fibrosis is recognized as the major pathological change in adipose tissue during the development of obesity. However, the detailed mechanisms governing the interactions between the fibrotic components and their modifiers remain largely unclear. Here, we reported that matrix metalloproteinase 14 (MMP14), a key pericellular collagenase, is dramatically upregulated in obese adipose tissue. We generated a doxycycline-inducible adipose tissue-specific MMP14 overexpression model to study its regulatory function. We found that overexpression of MMP14 in the established obese adipose tissue leads to enlarged adipocytes and increased body weights in transgenic mice. Furthermore, the mice exhibited decreased energy expenditure, impaired lipid metabolism, and insulin resistance. Mechanistically, we found that MMP14 digests collagen 6α3 to produce endotrophin, a potent costimulator of fibrosis and inflammation. Unexpectedly, when overexpressing MMP14 in the early-stage obese adipose tissue, the transgenic mice showed a healthier metabolic profile, including ameliorated fibrosis and inflammation, as well as improved lipid and glucose metabolism. This unique metabolic phenotype is likely due to digestion/modification of the dense adipose tissue extracellular matrix by MMP14, thereby releasing the mechanical stress to allow for its healthy expansion. Understanding these dichotomous impacts of MMP14 provides novel insights into strategies to treat obesity-related metabolic disorders.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Critical Role of Matrix Metalloproteinase 14 in Adipose Tissue Remodeling during Obesity

Zhao

Chen

et al. 2020

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…Endotrophin increases the proinflammatory cytokines and causes insulin resistance and also associated with pathologies such as diabetes mellitus, atherosclerosis, metabolic syndrome, and some cancers such as breast and colon cancers. 5,6 An increased number of studies conducted in recent years indicate that there is a chronic low level of inflammatory activity in PCOS. While some signal molecules secreted by leukocytes, oocyte, and follicular cells in the ovarian tissue regulate ovarian functions by paracrine and autocrine signals, molecules secreted from other tissues such as adipose tissue regulate ovarian functions by endocrine signals.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Endotrophin as a novel marker in PCOS and its relation with other adipokines and metabolic parameters: a pilot study

Güney

Taşkın

Baykan

et al. 2021

Therapeutic Advances in Endocrinology

View full text Add to dashboard Cite

Background: Polycystic ovary syndrome is known to be the most common hormonal disorder in women of reproductive age. Current evidence shows that regulatory proteins secreted from the adipose tissue called adipokines may have a role in polycystic ovary syndrome. We planned to investigate the role of endotrophin that has never been researched in polycystic ovary syndrome before and its correlation with other metabolic parameters and adipokines such as adiponectin and ghrelin in patients with polycystic ovary syndrome. Methods: Forty-three women ( n: 43) with polycystic ovary syndrome and 43 ( n: 43) women as a control group were enrolled in this cross-sectional study. Serum levels of endotrophin, adiponectin, and ghrelin levels were measured with the enzyme-linked immunosorbent assay method. High-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol levels, luteinizing hormone/follicle-stimulating hormone ratio, total testosterone, and triglyceride levels were measured. Homeostasis model assessment for insulin resistance index, body mass index, Ferriman Gallwey Score, and waist-to-hip ratio were also evaluated. Results: Total testosterone, homeostasis model assessment for insulin resistance, C-reactive protein, luteinizing hormone/follicle-stimulating hormone ratio, and triglyceride levels were higher in patients with polycystic ovary syndrome ( p < 0.01). No difference was detected between the groups in terms of body mass index, Ferriman Gallwey Score, waist-to-hip ratio, total cholesterol, low-density lipoprotein, and high-density lipoprotein levels ( p > 0.05). We did not observe any significant difference in adiponectin and ghrelin levels between the groups ( p > 0.05). Patients with polycystic ovary syndrome had significantly higher endotrophin levels ( p < 0.01). According to our regression analyses [area under the curve: 0.973 (0.935–1.000), 95% confidence interval, 95.2% sensitivity, and 100% specificity], it was shown that endotrophin greater than 92 ng/ml and homeostasis model assessment for insulin resistance greater than 2.5 might be good predictors for polycystic ovary syndrome diagnosis. Conclusion: We demonstrated that endotrophin level is higher in patients with polycystic ovary syndrome and may have predicted polycystic ovary syndrome with increased homeostasis model assessment for insulin resistance index. There was no significant difference in adiponectin and ghrelin levels in the polycystic ovary syndrome group. Endotrophin may have a role in polycystic ovary syndrome etiology rather than other adipokines.

show abstract

Extracellular Matrix (ECM) and Fibrosis in Adipose Tissue: Overview and Perspectives

Sun

Scherer

2023

Comprehensive Physiology

View full text Add to dashboard Cite

Serum endotrophin levels in patients with heart failure with reduced and mid-range ejection fraction

Cited by 8 publications

References 17 publications

Critical Role of Matrix Metalloproteinase 14 in Adipose Tissue Remodeling during Obesity

Critical Role of Matrix Metalloproteinase 14 in Adipose Tissue Remodeling during Obesity

Endotrophin as a novel marker in PCOS and its relation with other adipokines and metabolic parameters: a pilot study

Extracellular Matrix (ECM) and Fibrosis in Adipose Tissue: Overview and Perspectives

Contact Info

Product

Resources

About