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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
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 |
| Summary: | 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. |
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| ISSN: | 2049-3614 2049-3614 |