Liraglutide protects against high-fat diet-induced kidney injury by ameliorating apoptosis
Background: Obesity is associated with the development and progression of c hronic kidney disease. Emerging evidence suggests that glucagon-like p eptide-1 receptor agonist could reduce renal damage and albuminuria. Sirtuin 1 (S IRT1) was considered as a crucial regulator in metabolism-related kidne...
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| Format: | Article |
| Language: | English |
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Bioscientifica
2020-10-01
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| Series: | Endocrine Connections |
| Subjects: | |
| Online Access: | https://ec.bioscientifica.com/view/journals/ec/9/9/EC-20-0294.xml |
| _version_ | 1811267627631247360 |
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| author | Riying Liang Meijun Wang Chang Fu Hua Liang Hongrong Deng Ying Tan Fen Xu Mengyin Cai |
| author_facet | Riying Liang Meijun Wang Chang Fu Hua Liang Hongrong Deng Ying Tan Fen Xu Mengyin Cai |
| author_sort | Riying Liang |
| collection | DOAJ |
| description | Background: Obesity is associated with the development and progression of c hronic kidney disease. Emerging evidence suggests that glucagon-like p eptide-1 receptor agonist could reduce renal damage and albuminuria. Sirtuin 1 (S IRT1) was considered as a crucial regulator in metabolism-related kidney disease. He rein, the role of SIRT1 in liraglutide-ameliorated high-fat diet (HFD)-induced kidney injury was illustrated.
Methods: Male C57BL/6 mice were fed HFD for 20 weeks to induce kidney injury that was then treated with liraglutide for 8 weeks to estimate its prote ctive effect on the kidney. Also, the mechanism of the drug in SV40 MES 13 (SV40) mouse mes angial cells was elucidated.
Results: Liraglutide treatment ameliorated HFD-induced metabolic disorders, including hyperglycemia, increasing body weight, and insulin resistance. In addition, kidney weight, urine albumin-to-creatinine, and kidney morphological changes such as vacuolated tubules, glomerulomegaly, thickened glomerular basement membrane, and tubulointerstitial fibrosis were also significantly ameliorated. Furthermore, apoptotic cells and apoptosis markers were downregulated in the kidney of liraglutide-treated mice. In addition, the expression of SIRT1 protein was upregula ted, whereas thioredoxin-interacting protein (TXNIP), which serves as a mediator of oxid ative stress and apoptosis in metabolism disease, was downregulated by liraglutide. In SV4 0 cells, the effect of liraglutide on reversing the upregulation of cleaved caspase-3 induced by high glucose (30 mM) was hampered when SIRT1 was knocked down; also, the dow nregulation of TXNIP by liraglutide was blocked.
Conclusions: Liraglutide might have a beneficial effect on metabolism-relate d kidney damage by inhibiting apoptosis via activation of SIRT1 and supp ression of TXNIP pathway. |
| first_indexed | 2024-04-12T21:06:01Z |
| format | Article |
| id | doaj.art-8ab9070512dc4b0eaf34436c4a38cdbd |
| institution | Directory Open Access Journal |
| issn | 2049-3614 2049-3614 |
| language | English |
| last_indexed | 2024-04-12T21:06:01Z |
| publishDate | 2020-10-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrine Connections |
| spelling | doaj.art-8ab9070512dc4b0eaf34436c4a38cdbd2022-12-22T03:16:42ZengBioscientificaEndocrine Connections2049-36142049-36142020-10-0199946954https://doi.org/10.1530/EC-20-0294Liraglutide protects against high-fat diet-induced kidney injury by ameliorating apoptosisRiying Liang0Meijun Wang1Chang Fu2Hua Liang3Hongrong Deng4Ying Tan5Fen Xu6Mengyin Cai7Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China; Department of Ultrasound, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaDepartment of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, ChinaDepartment of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, ChinaDepartment of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, ChinaDepartment of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, ChinaDepartment of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, ChinaDepartment of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, ChinaDepartment of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, ChinaBackground: Obesity is associated with the development and progression of c hronic kidney disease. Emerging evidence suggests that glucagon-like p eptide-1 receptor agonist could reduce renal damage and albuminuria. Sirtuin 1 (S IRT1) was considered as a crucial regulator in metabolism-related kidney disease. He rein, the role of SIRT1 in liraglutide-ameliorated high-fat diet (HFD)-induced kidney injury was illustrated. Methods: Male C57BL/6 mice were fed HFD for 20 weeks to induce kidney injury that was then treated with liraglutide for 8 weeks to estimate its prote ctive effect on the kidney. Also, the mechanism of the drug in SV40 MES 13 (SV40) mouse mes angial cells was elucidated. Results: Liraglutide treatment ameliorated HFD-induced metabolic disorders, including hyperglycemia, increasing body weight, and insulin resistance. In addition, kidney weight, urine albumin-to-creatinine, and kidney morphological changes such as vacuolated tubules, glomerulomegaly, thickened glomerular basement membrane, and tubulointerstitial fibrosis were also significantly ameliorated. Furthermore, apoptotic cells and apoptosis markers were downregulated in the kidney of liraglutide-treated mice. In addition, the expression of SIRT1 protein was upregula ted, whereas thioredoxin-interacting protein (TXNIP), which serves as a mediator of oxid ative stress and apoptosis in metabolism disease, was downregulated by liraglutide. In SV4 0 cells, the effect of liraglutide on reversing the upregulation of cleaved caspase-3 induced by high glucose (30 mM) was hampered when SIRT1 was knocked down; also, the dow nregulation of TXNIP by liraglutide was blocked. Conclusions: Liraglutide might have a beneficial effect on metabolism-relate d kidney damage by inhibiting apoptosis via activation of SIRT1 and supp ression of TXNIP pathway.https://ec.bioscientifica.com/view/journals/ec/9/9/EC-20-0294.xmlchronic kidney diseaseglucagon-like peptide-1apoptosis |
| spellingShingle | Riying Liang Meijun Wang Chang Fu Hua Liang Hongrong Deng Ying Tan Fen Xu Mengyin Cai Liraglutide protects against high-fat diet-induced kidney injury by ameliorating apoptosis Endocrine Connections chronic kidney disease glucagon-like peptide-1 apoptosis |
| title | Liraglutide protects against high-fat diet-induced kidney injury by ameliorating apoptosis |
| title_full | Liraglutide protects against high-fat diet-induced kidney injury by ameliorating apoptosis |
| title_fullStr | Liraglutide protects against high-fat diet-induced kidney injury by ameliorating apoptosis |
| title_full_unstemmed | Liraglutide protects against high-fat diet-induced kidney injury by ameliorating apoptosis |
| title_short | Liraglutide protects against high-fat diet-induced kidney injury by ameliorating apoptosis |
| title_sort | liraglutide protects against high fat diet induced kidney injury by ameliorating apoptosis |
| topic | chronic kidney disease glucagon-like peptide-1 apoptosis |
| url | https://ec.bioscientifica.com/view/journals/ec/9/9/EC-20-0294.xml |
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