Endothelin-1 in the pathophysiology of obesity and insulin resistance

Obes Rev. 2020 Dec;21(12):e13086. doi: 10.1111/obr.13086. Epub 2020 Jul 6.

Abstract

The association between plasma endothelin-1 (ET-1) and obesity has been documented for decades, yet the contribution of ET-1 to risk factors associated with obesity is not fully understood. In 1994, one of first papers to document this association also noted a positive correlation between plasma insulin and ET-1, suggesting a potential contribution of ET-1 to the development of insulin resistance. Both endogenous receptors for ET-1, ETA and ETB are present in all insulin-sensitive tissues including adipose, liver and muscle, and ET-1 actions within these tissues suggest that ET-1 may be playing a role in the pathogenesis of insulin resistance. Further, antagonists for ET-1 receptors are clinically approved making these sites attractive therapeutic targets. This review focuses on known mechanisms through which ET-1 affects plasma lipid profiles and insulin signalling in these metabolically important tissues and also identifies gaps in our understanding of ET-1 in obesity-related pathophysiology.

Keywords: ET-1; insulin resistance; obesity.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Endothelin-1* / physiology
  • Humans
  • Insulin Resistance*
  • Obesity / physiopathology*
  • Receptor, Endothelin A / physiology

Substances

  • Endothelin-1
  • Receptor, Endothelin A