{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Rivera-Gonzalez O"],"funding":["NIDDK NIH HHS","NHLBI NIH HHS","NIGMS NIH HHS"],"pagination":["e14214"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11421981"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["240(10)"],"pubmed_abstract":["<h4>Aims</h4>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<sub>B</sub>) improves insulin sensitivity in rats and leads to increased circulating adiponectin, suggesting that ET<sub>B</sub> 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<sub>B</sub> receptor.<h4>Methods</h4>Male adipocyte-specific ET<sub>B</sub> receptor knockout (adET<sub>B</sub>KO), overexpression (adET<sub>B</sub>OX), or control littermates were fed either normal diet (NMD) or high-fat diet (HFD) for 8 weeks.<h4>Results</h4>RNA-sequencing of epididymal adipose (eWAT) indicated differential expression of over 5500 genes (p < 0.05) in HFD compared to NMD controls, and changes in 1077 of these genes were attenuated in HFD adET<sub>B</sub>KO mice. KEGG analysis indicated significant increase in metabolic signaling pathway. HFD adET<sub>B</sub>KO mice had significantly improved glucose and insulin tolerance compared to HFD control. In addition, adET<sub>B</sub>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<sub>B</sub> antagonist.<h4>Conclusion</h4>These data indicate elevated ET-1 in adipose tissue of mice fed HFD inhibits adiponectin production and causes insulin resistance through activation of the ET<sub>B</sub> receptor on adipocytes."],"journal":["Acta physiologica (Oxford, England)"],"pubmed_title":["Adipocyte endothelin B receptor activation inhibits adiponectin production and causes insulin resistance in obese mice."],"pmcid":["PMC11421981"],"funding_grant_id":["U2C DK133422","P20 GM144041","P30 GM149404","P01 HL158500","R01 DK124327","P20 GM104357","T32 HL105324","F31 DK125035","P20 GM103476","R01 DK126664","U54 GM115428"],"pubmed_authors":["Garrett MR","Speed JS","Wilson NA","Webb DJ","Rivera-Gonzalez O","Konadu BD","Murphy HA","Mills MF","Hyndman KA","Newberry MK"],"additional_accession":[]},"is_claimable":false,"name":"Adipocyte endothelin B receptor activation inhibits adiponectin production and causes insulin resistance in obese mice.","description":"<h4>Aims</h4>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<sub>B</sub>) improves insulin sensitivity in rats and leads to increased circulating adiponectin, suggesting that ET<sub>B</sub> 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<sub>B</sub> receptor.<h4>Methods</h4>Male adipocyte-specific ET<sub>B</sub> receptor knockout (adET<sub>B</sub>KO), overexpression (adET<sub>B</sub>OX), or control littermates were fed either normal diet (NMD) or high-fat diet (HFD) for 8 weeks.<h4>Results</h4>RNA-sequencing of epididymal adipose (eWAT) indicated differential expression of over 5500 genes (p < 0.05) in HFD compared to NMD controls, and changes in 1077 of these genes were attenuated in HFD adET<sub>B</sub>KO mice. KEGG analysis indicated significant increase in metabolic signaling pathway. HFD adET<sub>B</sub>KO mice had significantly improved glucose and insulin tolerance compared to HFD control. In addition, adET<sub>B</sub>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<sub>B</sub> antagonist.<h4>Conclusion</h4>These data indicate elevated ET-1 in adipose tissue of mice fed HFD inhibits adiponectin production and causes insulin resistance through activation of the ET<sub>B</sub> receptor on adipocytes.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Oct","modification":"2026-06-03T23:18:51.783Z","creation":"2026-05-03T03:10:24.72Z"},"accession":"S-EPMC11421981","cross_references":{"pubmed":["39096077"],"doi":["10.1111/apha.14214"]}}