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Abstract: TH-PO0273

Liraglutide, a GLP-1 Receptor Agonist, Improves Metabolic Profile and Kidney Function in a Rat Model of Obesity-Induced Kidney Injury

Session Information

Category: Hypertension and CVD

  • 1601 Hypertension and CVD: Basic

Authors

  • Oliveira, Julia Cristine, Universidade Federal de Sao Paulo, São Paulo, SP, Brazil
  • de Castro Barbosa, Gabrielle Regis, Universidade Federal de Sao Paulo, São Paulo, SP, Brazil
  • Silva, Eric Rafael Andrade, Universidade Federal de Sao Paulo, São Paulo, SP, Brazil
  • Ferreira, Erick Jamarino Diniz, Universidade Federal de Sao Paulo, São Paulo, SP, Brazil
  • Cesaretti, Mario Luis Ribeiro, Universidade Federal de Sao Paulo, São Paulo, SP, Brazil
  • Batista, Marcelo Costa, Universidade Federal de Sao Paulo, São Paulo, SP, Brazil

Group or Team Name

  • LORDc - UNIFESP.
Background

Insulin resistance, visceral obesity, and hypertension are major cardiovascular risk factors that also contribute to the development of chronic kidney disease (CKD) through metabolic dysregulation and systemic inflammation. Glucagon-like peptide-1 (GLP-1) receptor agonists, such as liraglutide, have demonstrated potential renoprotective and cardioprotective effects. This study investigated the impact of liraglutide on metabolic parameters, inflammatory markers, and renal function in spontaneously hypertensive rats (SHRs) fed a hypercaloric diet.

Methods

SHRs were randomized into four groups: G1 – control (standard diet), G2 – hypercaloric diet, G3 – standard diet + liraglutide, and G4 – hypercaloric diet + liraglutide. Liraglutide was administered daily for 12 weeks. Assessments included glucose tolerance test (GTT), insulin tolerance test (ITT), body weight, systolic blood pressure, serum biochemistry, and renal histopathology. Circulating levels of inflammatory cytokines (IL-6, TNF-α, IL-1β, IL-10, TGF-β), lipocalin-2 (NGAL), glucose-dependent insulinotropic polypeptide (GIP), and HIF1α were measured by ELISA.

Results

Liraglutide treatment in G4 significantly reduced body weight and systolic blood pressure compared to G2 (p<0.01). G4 also exhibited improved glucose handling in both GTT and ITT, and a marked reduction in total and visceral adiposity. Serum creatinine was significantly lower in G4 compared to G2 (0.65±0.03 vs. 0.801±0.094 mg/dL, p=0.002), along with an improved cholesterol profile. Levels of TGF-β and HIF1α were attenuated in G4. NGAL, an early biomarker of tubular injury, was significantly reduced in G4 (6.25±1.92 ng/mL) compared to G2 (27.57±2.59 ng/mL, p<0.001). Additionally, liraglutide lowered proinflammatory cytokines and restored IL-10 levels.

Conclusion

Liraglutide effectively mitigates obesity-related metabolic disturbances, systemic inflammation, and renal injury in a hypertensive rat model. These findings underscore the potential therapeutic role of GLP-1 receptor agonists in the management of obesity-associated kidney disease.

Funding

  • Government Support – Non-U.S.

Digital Object Identifier (DOI)