Tripeptide IRW Improves AMPK/eNOS Signaling Pathway via Activating ACE2 in the Aorta of High-Fat-Diet-Fed C57BL/6 Mice
This study aims to investigate the effect of tripeptide IRW on the local renin–angiotensin system (RAS), particularly angiotensin-converting enzyme 2 (ACE2), and their association with signaling pathways in the aorta of a high-fat-diet (HFD)-induced insulin-resistant mouse model. C57BL/6 mice were f...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/12/4/556 |
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| author | Fatemeh Ashkar Khushwant S. Bhullar Xu Jiang Jianping Wu |
| author_facet | Fatemeh Ashkar Khushwant S. Bhullar Xu Jiang Jianping Wu |
| author_sort | Fatemeh Ashkar |
| collection | DOAJ |
| description | This study aims to investigate the effect of tripeptide IRW on the local renin–angiotensin system (RAS), particularly angiotensin-converting enzyme 2 (ACE2), and their association with signaling pathways in the aorta of a high-fat-diet (HFD)-induced insulin-resistant mouse model. C57BL/6 mice were fed HFD (45% of the total calories) for six weeks, and then IRW was added to the diet (45 mg/kg body weight (BW)) for another eight weeks. ACE2 mRNA expression and protein level(s) were increased (<i>p</i> < 0.05), while angiotensin II receptor (AT1R) and angiotensin-converting enzyme (ACE) protein abundance was significantly reduced (<i>p</i> < 0.05) in the aorta of HFD mice treated by IRW. IRW supplementation also improved glucose transporter 4 (GLUT4) abundance (<i>p</i> < 0.05) alongside AMP-activated protein kinase (AMPK) (<i>p</i> < 0.05), Sirtuin 1 (SIRT1) (<i>p</i> < 0.05), and endothelial nitric oxide synthase (eNOS) (<i>p</i> < 0.05) expression. IRW downregulated the levels of endothelin 1 (ET-1) and p38 mitogen-activated protein kinases (p38 MAPK, <i>p</i> < 0.05). Furthermore, the levels of AMPK and eNOS in vascular smooth muscle cells (VSMCs) were significantly reduced in ACE2 knockdown cells treated with or without IRW (<i>p</i> < 0.01). In conclusion, this study provided new evidence of the regulatory role of IRW on the aortic ACE2 against metabolic syndrome (MetS) in an HFD-induced insulin-resistant model. |
| first_indexed | 2024-03-11T05:13:38Z |
| format | Article |
| id | doaj.art-0650cb96a2a54503adee9f88c68bd6dd |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-11T05:13:38Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-0650cb96a2a54503adee9f88c68bd6dd2023-11-17T18:23:55ZengMDPI AGBiology2079-77372023-04-0112455610.3390/biology12040556Tripeptide IRW Improves AMPK/eNOS Signaling Pathway via Activating ACE2 in the Aorta of High-Fat-Diet-Fed C57BL/6 MiceFatemeh Ashkar0Khushwant S. Bhullar1Xu Jiang2Jianping Wu3Department of Agricultural Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, CanadaDepartment of Agricultural Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, CanadaDepartment of Agricultural Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, CanadaDepartment of Agricultural Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, CanadaThis study aims to investigate the effect of tripeptide IRW on the local renin–angiotensin system (RAS), particularly angiotensin-converting enzyme 2 (ACE2), and their association with signaling pathways in the aorta of a high-fat-diet (HFD)-induced insulin-resistant mouse model. C57BL/6 mice were fed HFD (45% of the total calories) for six weeks, and then IRW was added to the diet (45 mg/kg body weight (BW)) for another eight weeks. ACE2 mRNA expression and protein level(s) were increased (<i>p</i> < 0.05), while angiotensin II receptor (AT1R) and angiotensin-converting enzyme (ACE) protein abundance was significantly reduced (<i>p</i> < 0.05) in the aorta of HFD mice treated by IRW. IRW supplementation also improved glucose transporter 4 (GLUT4) abundance (<i>p</i> < 0.05) alongside AMP-activated protein kinase (AMPK) (<i>p</i> < 0.05), Sirtuin 1 (SIRT1) (<i>p</i> < 0.05), and endothelial nitric oxide synthase (eNOS) (<i>p</i> < 0.05) expression. IRW downregulated the levels of endothelin 1 (ET-1) and p38 mitogen-activated protein kinases (p38 MAPK, <i>p</i> < 0.05). Furthermore, the levels of AMPK and eNOS in vascular smooth muscle cells (VSMCs) were significantly reduced in ACE2 knockdown cells treated with or without IRW (<i>p</i> < 0.01). In conclusion, this study provided new evidence of the regulatory role of IRW on the aortic ACE2 against metabolic syndrome (MetS) in an HFD-induced insulin-resistant model.https://www.mdpi.com/2079-7737/12/4/556IRWinsulin resistanceGLUT4eNOSACE2peptides |
| spellingShingle | Fatemeh Ashkar Khushwant S. Bhullar Xu Jiang Jianping Wu Tripeptide IRW Improves AMPK/eNOS Signaling Pathway via Activating ACE2 in the Aorta of High-Fat-Diet-Fed C57BL/6 Mice Biology IRW insulin resistance GLUT4 eNOS ACE2 peptides |
| title | Tripeptide IRW Improves AMPK/eNOS Signaling Pathway via Activating ACE2 in the Aorta of High-Fat-Diet-Fed C57BL/6 Mice |
| title_full | Tripeptide IRW Improves AMPK/eNOS Signaling Pathway via Activating ACE2 in the Aorta of High-Fat-Diet-Fed C57BL/6 Mice |
| title_fullStr | Tripeptide IRW Improves AMPK/eNOS Signaling Pathway via Activating ACE2 in the Aorta of High-Fat-Diet-Fed C57BL/6 Mice |
| title_full_unstemmed | Tripeptide IRW Improves AMPK/eNOS Signaling Pathway via Activating ACE2 in the Aorta of High-Fat-Diet-Fed C57BL/6 Mice |
| title_short | Tripeptide IRW Improves AMPK/eNOS Signaling Pathway via Activating ACE2 in the Aorta of High-Fat-Diet-Fed C57BL/6 Mice |
| title_sort | tripeptide irw improves ampk enos signaling pathway via activating ace2 in the aorta of high fat diet fed c57bl 6 mice |
| topic | IRW insulin resistance GLUT4 eNOS ACE2 peptides |
| url | https://www.mdpi.com/2079-7737/12/4/556 |
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