Abstract: PUB393
Metformin Attenuates Oxidative Stress and Inflammatory Responses in Obesity-Associated Nonalcoholic Fatty Liver Disease (NAFLD)
Session Information
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Sharma, Amod, University of Arkansas for Medical Sciences College of Medicine, Little Rock, Arkansas, United States
- Hakkak, Reza, University of Arkansas for Medical Sciences College of Medicine, Little Rock, Arkansas, United States
- Gokden, Neriman, University of Arkansas for Medical Sciences College of Medicine, Little Rock, Arkansas, United States
- Parajuli, Nirmala, University of Arkansas for Medical Sciences College of Medicine, Little Rock, Arkansas, United States
Background
Chronic kidney disease (CKD) is significantly more prevalent in individuals with obesity-associated non-alcoholic fatty liver disease (Ob-NAFLD), yet the mechanisms linking these conditions remain poorly understood. This study investigates the renal consequences of Ob-NAFLD and evaluates the potential protective effects of metformin, a widely used antidiabetic drug with emerging therapeutic value in NAFLD.
Methods
Five-week-old female Zucker rats (obese fa/fa and lean Fa/Fa) were fed a standard diet for 8 weeks to induce obesity NAFLD (Ob-NAFLD) followed by oral treatment with metformin (1 g/kg food, ad libitum) for 10 weeks. Kidneys were harvested and analyzed histologically and biochemically.
Results
Ob-NAFLD rats showed significant renal damage, including tubular injury, mesangial expansion, and fibrosis compared to lean rats. Similarly, Ob-NAFLD rats showed elevated macrophage and neutrophil infiltration, upregulated inflammatory genes (TNF-α and CCL2), and increased markers of mitochondrial fission (DRP1 and phospho-DRP1), oxidative stress (nitrotyrosine, p22phox), and apoptosis (caspase-3), compared to lean group. Low dose oral metformin treatment significantly reduced inflammation (TNF-α) and oxidative stress (nitrotyrosine) but was inadequate to preserve renal morphology in rat kidneys with Ob-NAFLD.
Conclusion
Altogether, these findings suggest that Ob-NAFLD drives CKD via inflammation and oxidative/mitochondrial stress. While metformin offers anti-inflammatory and antioxidant benefits, longer treatment or combination therapies may be needed for renal protection.
Funding: Arkansas Bioscience Institute (Hakkak) and R01DK123264 (Parajuli).
Funding
- NIDDK Support