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

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

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 B ) improves insulin sensitivity in rats and leads to increased circulating adiponectin, suggesting that ET B 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 B receptor. Methods Male adipocyte-specific ET B receptor knockout (adET B KO), overexpression (adET B OX), or control littermates were fed either normal diet (NMD) or high-fat diet (HFD) for 8 weeks. Results RNA-sequencing of epididymal adipose (eWAT) indicated differential expression of over 5500 genes (p B KO mice. KEGG analysis indicated significant increase in metabolic signaling pathway. HFD adET B KO mice had significantly improved glucose and insulin tolerance compared to HFD control. In addition, adET B KO attenuated changes in plasma adiponectin, insulin, and leptin that is observed in HFD versus NMD control mice. Treatment of primary adipocytes with ET-1 caused a reduction in adiponectin production that was attenuated in cells pretreated with an ET B antagonist. Conclusion These data indicate elevated ET-

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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