Liraglutide Protects Kidneys from Obesity Damage by Regulating the CaMKKβ/AMPK Pathway in Mice

Liraglutide (0.6 mg/kg for 12 weeks) protected against HFD-induced kidney injury by reducing serum lipids, improving kidney function markers, reversing kidney pathology, and inhibiting the CaMKKβ/AMPK signaling pathway. Bortezomib (AMPK agonist) partially reversed these effects.

36 C57BL/6J male mice in 6 groups (n=6). Obesity-related kidney disease induced by 12 weeks HFD, then 12 weeks of liraglutide (0.6 mg/kg) or bortezomib (200 μg/kg). Measured serum lipids, kidney function (Scr, BUN, urinary protein), kidney histology (H&E, PAS staining), and CaMKKβ/AMPK pathway activation (IHC, western blot, RT-qPCR).

Obesity-related kidney disease is a growing epidemic with no targeted treatment. Demonstrating that liraglutide directly protects kidneys through a defined molecular pathway (not just through weight loss) could expand its clinical indications to include kidney protection in obese patients.

GLP-1 agonists continue to reveal organ-protective effects beyond glucose control. The kidney protection via CaMKKβ/AMPK pathway adds to evidence of cardiovascular, liver, and brain protection — building the case that GLP-1 agonists are multi-organ protective drugs.

Small animal study (6 mice per group). Only 12 weeks of treatment may not capture long-term kidney outcomes. The use of bortezomib (primarily a proteasome inhibitor) as an AMPK agonist adds complexity to interpretation. Human kidney disease involves factors beyond what HFD models capture.