Intricacies of the endothelin system in human obesity: Role in the development of complications and potential as a therapeutic target

Francesca Schinzari, Carmine Cardillo

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

Abstract

Activation of the vascular endothelin-1 (ET-1) system is a key abnormality in vascular dysfunction of human obesity, especially in patients developing complications, such as the metabolic syndrome, diabetes, and atherosclerosis. Vascular insulin resistance, an increased insulin-stimulated endothelial production of ET-1 combined with impaired nitric oxide availability, is the hallmark of obesity-related vasculopathy, but dysregulated adipokine release from obese adipose tissue may contribute to the predominance of ET-1-dependent vasoconstriction. ET-1, in turn, might determine unhealthy obese adipose tissue expansion, with visceral and perivascular adipose tissue changes driving the release of inflammatory cytokines and atherogenic chemo-kines. In addition, ET-1 might also play a role in the development of the metabolic complications of obesity. Studies have shown inhibition of lipoprotein lipase activity by ET-1, with consequent hypertriglyceridemia. Also, ET-1 in pancreatic islets seems to contribute to beta cell dysfunction, hence affecting insulin production and development of diabetes. Moreover, ET-1 may play a role in nonalcoholic steatohepatitis. Recent clinical trials using innovative design have demonstrated that antagonism of ET-type A receptors protects against some complications of obesity and diabetes, such as nephropathy. These findings encourage further investigation to evaluate whether targeting the ET-1 system could afford better protection against other consequences of the obesity epidemic.
Lingua originaleEnglish
pagine (da-a)563-569
Numero di pagine7
RivistaCanadian Journal of Physiology and Pharmacology
Volume98
DOI
Stato di pubblicazionePubblicato - 2020

Keywords

  • Adipokines
  • Adipose Tissue
  • Adipose tissue
  • Cytokines
  • Diabetes Mellitus, Type 2
  • Diabetic Nephropathies
  • Dyslipidemia
  • Endothelin
  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Endothelium, Vascular
  • Humans
  • Insulin
  • Insulin Resistance
  • Insulin-Secreting Cells
  • NASH
  • Non-alcoholic Fatty Liver Disease
  • Obesity
  • Prediabetes
  • Receptor, Endothelin A
  • Vasoconstriction

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