Overproduction of endothelin-1 impairs glucose tolerance but does not promote visceral adipose tissue inflammation or limit metabolic adaptations to exercise.

Overproduction of endothelin-1 impairs glucose tolerance but does not promote visceral adipose tissue inflammation or limit metabolic adaptations to exercise. Am J Physiol Endocrinol Metab. 2019 Jul 16;: Authors: Jurrissen TJ, Grunewald ZI, Woodford ML, Winn NC, Ball JR, Smith TN, Wheeler A, Rawlings AL, Staveley-O'Carroll KF, Ji Y, Fay WP, Paradis P, Schiffrin EL, Vieira-Potter VJ, Fadel PJ, Martinez-Lemus LA, Padilla J Abstract Endothelin-1 (ET-1) is a potent vasoconstrictor and proinflammatory peptide that is upregulated in obesity. Herein, we tested the hypothesis that ET-1 signaling promotes visceral adipose tissue (AT) inflammation and disrupts glucose homeostasis. We also tested if reduced ET-1 is a required mechanism by which exercise ameliorates AT inflammation and improves glycemic control in obesity. We found that (i) diet-induced obesity, AT inflammation, and glycemic dysregulation were not accompanied by significant increased levels of ET-1 in AT or circulation in wild-type mice; and that endothelial overexpression of ET-1 and consequent increased ET-1 levels did not cause AT inflammation yet impaired glucose tolerance; (ii) reduced AT inflammation and improved glucose tolerance with voluntary wheel running was not associated with decreased levels of ET-1 in AT or circulation in obese mice, nor did endothelial overexpression of ET-1 impede such exercise-induced metabolic adaptations; (iii) chronic pharmacological blockad...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research