دورية أكاديمية
Endothelin receptor antagonism improves glucose handling, dyslipidemia, and adipose tissue inflammation in obese mice.
| العنوان: | Endothelin receptor antagonism improves glucose handling, dyslipidemia, and adipose tissue inflammation in obese mice. |
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| المؤلفون: | Rivera-Gonzalez O; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, U.S.A., Wilson NA; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, U.S.A., Coats LE; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, U.S.A., Taylor EB; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, U.S.A., Speed JS; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, U.S.A. |
| المصدر: | Clinical science (London, England : 1979) [Clin Sci (Lond)] 2021 Jul 30; Vol. 135 (14), pp. 1773-1789. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Portland Press on behalf of the Medical Research Society and the Biochemical Society Country of Publication: England NLM ID: 7905731 Publication Model: Print Cited Medium: Internet ISSN: 1470-8736 (Electronic) Linking ISSN: 01435221 NLM ISO Abbreviation: Clin Sci (Lond) Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: London : Portland Press on behalf of the Medical Research Society and the Biochemical Society Original Publication: London, Medical Research Society. |
| مواضيع طبية MeSH: | Dyslipidemias/*metabolism , Endothelin Receptor Antagonists/*pharmacology , Glucose/*metabolism , Inflammation/*metabolism , Obesity/*metabolism, Adipose Tissue/metabolism ; Animals ; Diet, High-Fat/methods ; Endothelin A Receptor Antagonists/pharmacology ; Insulin Resistance/physiology ; Liver/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Obese |
| مستخلص: | Endothelin-1 (ET-1) is elevated in patients with obesity; however, its contribution to the pathophysiology related to obesity is not fully understood. We hypothesized that high ET-1 levels cause dyslipidemia, inflammation, and insulin resistance within the adipose tissue of obese mice. To test this hypothesis, male C57BL/6J mice were fed either normal diet (NMD) or high-fat diet (HFD) for 8 weeks followed by 2 weeks of treatment with either vehicle, atrasentan (ETA receptor antagonist, 10 mg/kg/day) or bosentan (ETA/ETB receptor antagonist, 100 mg/kg/day). Atrasentan and bosentan lowered circulating non-esterified free fatty acids and triglycerides seen in HFD mice, while atrasentan-treated mice had significantly lower liver triglycerides compared with non-treated HFD mice. ET-1 receptor blockade significantly improved insulin tolerance compared with insulin-resistant HFD mice and lowered expression of genes in epididymal white adipose tissue (eWAT) associated with insulin resistance and inflammation. Flow cytometric analyses of eWAT indicated that HFD mice had significantly higher percentages of both CD4+ and CD8+ T cells compared with NMD mice, which was attenuated by treatment with atrasentan or bosentan. Atrasentan treatment also abolished the decrease in eosinophils seen in HFD mice. Taken together, these data indicate that ETA and ETA/ETB receptor blockade improves peripheral glucose homeostasis, dyslipidemia and liver triglycerides, and also attenuates the pro-inflammatory immune profile in eWAT of mice fed HFD. These data suggest a potential use for ETA and ETA/ETB receptor blockers in the treatment of obesity-associated dyslipidemia and insulin resistance. (© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.) |
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| معلومات مُعتمدة: | P20 GM103476 United States GM NIGMS NIH HHS; F31 DK125035 United States DK NIDDK NIH HHS; P20 GM104357 United States GM NIGMS NIH HHS; K99 HL146888 United States HL NHLBI NIH HHS; R00 HL127178 United States HL NHLBI NIH HHS; R01 DK124327 United States DK NIDDK NIH HHS; R25 HL121042 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Keywords: endothelins; inflammation; insulin resistance; obesity |
| المشرفين على المادة: | 0 (Endothelin A Receptor Antagonists) 0 (Endothelin Receptor Antagonists) IY9XDZ35W2 (Glucose) |
| تواريخ الأحداث: | Date Created: 20210719 Date Completed: 20211117 Latest Revision: 20231108 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC8650556 |
| DOI: | 10.1042/CS20210549 |
| PMID: | 34278410 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1470-8736 |
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| DOI: | 10.1042/CS20210549 |