Liraglutide alleviates high-fat diet-induced kidney injury in mice by regulating the CaMKKβ/AMPK pathway

• Published in: Renal failure 2024-12, Vol.46 (1), p.2351473
• Main Authors: Xuan, Yingli, Ding, Ting-Ting, Mao, Xiao-Lei, Pang, Shiqing, He, Ruibin, Qin, Li, Yuan, Jiang Zi
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury; Agonists; AMP-activated protein kinase; AMP-Activated Protein Kinases - metabolism; Animals; Body weight; Bortezomib; Calcium-Calmodulin-Dependent Protein Kinase Kinase - metabolism; Calmodulin; CaMKKβ/AMPK signaling pathway; Cholesterol; Creatinine; Diet, High-Fat - adverse effects; Disease Models, Animal; Enzyme-linked immunosorbent assay; Glucagon; Glucagon-like peptide 1; Glycogen; High fat diet; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Immunohistochemistry; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Kidney diseases; Kinases; Liraglutide; Liraglutide - pharmacology; Liraglutide - therapeutic use; Male; Mice; Mice, Inbred C57BL; Nephropathy; Obesity; Obesity - complications; Obesity - drug therapy; obesity-related kidney disease; Proteins; Signal transduction; Signal Transduction - drug effects; Triglycerides
• ISSN: 0886-022X; 1525-6049; 1525-6049
• DOI: 10.1080/0886022X.2024.2351473

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. Thirty-six C57BL/6J male mice were randomly divided into six groups (  = 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. 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. 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.