Adipocyte endothelin B receptor activation inhibits adiponectin production and causes insulin resistance in obese mice.

Aims: Endothelin-1 (ET-1) is elevated in patients with obesity and adipose tissue of obese mice fed high-fat diet (HFD); however, its contribution to the pathophysiology of obesity is not fully understood. Genetic loss of endothelin type B receptors (ET) improves insulin sensitivity in rats and leads to increased circulating adiponectin, suggesting that ET activation on adipocytes may contribute to obesity pathophysiology. We hypothesized that elevated ET-1 in obesity promotes insulin resistance by reducing the secretion of insulin sensitizing adipokines, via ET receptor.