Liraglutide alleviates high-fat diet-induced kidney injury in mice by regulating the CaMKKβ/AMPK pathway
Objective Liraglutide, a glucagon-like peptide-1 receptor agonist, has been shown to regulate blood sugar and control body weight, but its ability to treat obesity-related nephropathy has been poorly studied. Therefore, this study was designed to observe the characteristics and potential mechanism o...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2351473 |
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| author | Yingli Xuan Ting-ting Ding Xiao-lei Mao Shiqing Pang Ruibin He Li Qin Jiang zi Yuan |
| author_facet | Yingli Xuan Ting-ting Ding Xiao-lei Mao Shiqing Pang Ruibin He Li Qin Jiang zi Yuan |
| author_sort | Yingli Xuan |
| collection | DOAJ |
| description | Objective Liraglutide, a glucagon-like peptide-1 receptor agonist, has been shown to regulate blood sugar and control body weight, but its ability to treat obesity-related nephropathy has been poorly studied. Therefore, this study was designed to observe the characteristics and potential mechanism of liraglutide against obesity-related kidney disease.Methods Thirty-six C57BL/6J male mice were randomly divided into six groups (n = 6 per group). Obesity-related nephropathy was induced in mice by continuous feeding of high-fat diet (HFD) for 12 weeks. After 12 weeks, liraglutide (0.6 mg/kg) and AMP-activated protein kinase (AMPK) agonists bortezomib (200 μg/kg) were injected for 12 weeks, respectively. Enzyme-linked immunosorbent assay was employed to detect the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, blood urea nitrogen, creatinine in serum, as well as urinary protein in urine. Besides, hematoxylin–eosin staining and periodic acid-Schiff staining were used to observe the pathological changes of kidney tissue; immunohistochemistry, western blot, and real-time quantitative PCR to assess the calmodulin-dependent protein kinase kinase beta (CaMKKβ)/AMPK signaling pathway activation.Results Liraglutide significantly reduced serum lipid loading, improved kidney function, and relieved kidney histopathological damage and glycogen deposition in the mouse model of obesity-related kidney disease induced by HFD. In addition, liraglutide also significantly inhibited the CaMKKβ/AMPK signaling pathway in kidney tissue of HFD-induced mice. However, bortezomib partially reversed the therapeutic effect of liraglutide on HDF-induced nephropathy in mice.Conclusions Liraglutide has a therapeutic effect on obesity-related kidney disease, and such an effect may be achieved by inhibiting the CaMKKβ/AMPK signaling pathway in kidney tissue. |
| format | Article |
| id | doaj-art-ce39ac4468a24c868423c11c1d2c3624 |
| institution | Kabale University |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-ce39ac4468a24c868423c11c1d2c36242025-01-23T04:17:49ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146110.1080/0886022X.2024.2351473Liraglutide alleviates high-fat diet-induced kidney injury in mice by regulating the CaMKKβ/AMPK pathwayYingli Xuan0Ting-ting Ding1Xiao-lei Mao2Shiqing Pang3Ruibin He4Li Qin5Jiang zi Yuan6Department of Nephrology, School of Medicine, Baoshan Branch of Renji Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Nephrology, School of Medicine, Baoshan Branch of Renji Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Nephrology, School of Medicine, Baoshan Branch of Renji Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Nephrology, School of Medicine, Baoshan Branch of Renji Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Nephrology, School of Medicine, Baoshan Branch of Renji Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Nephrology, School of Medicine, Baoshan Branch of Renji Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Nephrology, School of Medicine, Baoshan Branch of Renji Hospital, Shanghai Jiao Tong University, Shanghai, ChinaObjective Liraglutide, a glucagon-like peptide-1 receptor agonist, has been shown to regulate blood sugar and control body weight, but its ability to treat obesity-related nephropathy has been poorly studied. Therefore, this study was designed to observe the characteristics and potential mechanism of liraglutide against obesity-related kidney disease.Methods Thirty-six C57BL/6J male mice were randomly divided into six groups (n = 6 per group). Obesity-related nephropathy was induced in mice by continuous feeding of high-fat diet (HFD) for 12 weeks. After 12 weeks, liraglutide (0.6 mg/kg) and AMP-activated protein kinase (AMPK) agonists bortezomib (200 μg/kg) were injected for 12 weeks, respectively. Enzyme-linked immunosorbent assay was employed to detect the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, blood urea nitrogen, creatinine in serum, as well as urinary protein in urine. Besides, hematoxylin–eosin staining and periodic acid-Schiff staining were used to observe the pathological changes of kidney tissue; immunohistochemistry, western blot, and real-time quantitative PCR to assess the calmodulin-dependent protein kinase kinase beta (CaMKKβ)/AMPK signaling pathway activation.Results Liraglutide significantly reduced serum lipid loading, improved kidney function, and relieved kidney histopathological damage and glycogen deposition in the mouse model of obesity-related kidney disease induced by HFD. In addition, liraglutide also significantly inhibited the CaMKKβ/AMPK signaling pathway in kidney tissue of HFD-induced mice. However, bortezomib partially reversed the therapeutic effect of liraglutide on HDF-induced nephropathy in mice.Conclusions Liraglutide has a therapeutic effect on obesity-related kidney disease, and such an effect may be achieved by inhibiting the CaMKKβ/AMPK signaling pathway in kidney tissue.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2351473Liraglutidehigh-fat dietobesity-related kidney diseaseCaMKKβ/AMPK signaling pathway |
| spellingShingle | Yingli Xuan Ting-ting Ding Xiao-lei Mao Shiqing Pang Ruibin He Li Qin Jiang zi Yuan Liraglutide alleviates high-fat diet-induced kidney injury in mice by regulating the CaMKKβ/AMPK pathway Renal Failure Liraglutide high-fat diet obesity-related kidney disease CaMKKβ/AMPK signaling pathway |
| title | Liraglutide alleviates high-fat diet-induced kidney injury in mice by regulating the CaMKKβ/AMPK pathway |
| title_full | Liraglutide alleviates high-fat diet-induced kidney injury in mice by regulating the CaMKKβ/AMPK pathway |
| title_fullStr | Liraglutide alleviates high-fat diet-induced kidney injury in mice by regulating the CaMKKβ/AMPK pathway |
| title_full_unstemmed | Liraglutide alleviates high-fat diet-induced kidney injury in mice by regulating the CaMKKβ/AMPK pathway |
| title_short | Liraglutide alleviates high-fat diet-induced kidney injury in mice by regulating the CaMKKβ/AMPK pathway |
| title_sort | liraglutide alleviates high fat diet induced kidney injury in mice by regulating the camkkβ ampk pathway |
| topic | Liraglutide high-fat diet obesity-related kidney disease CaMKKβ/AMPK signaling pathway |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2351473 |
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