Impact of Combination Therapy With Caffeine and Naringin on Insulin Resistance and Renal Function in a Nonalcoholic Fatty Liver Disease Rat Model.

INTRODUCTION: Chronic kidney disease (CKD) is a major global health concern, and evidence indicates that non-alcoholic fatty liver disease (NAFLD) independently increases its risk and progression. This connection involves shared pathways such as chronic inflammation, oxidative stress, and insulin resistance, which can worsen renal injury. Caffeine (CAF) and naringin (NAR), with their antioxidant and anti-inflammatory properties, may provide protective effects on both NAFLD and CKD. This study evaluated the impact of combined CAF and NAR treatment on insulin resistance and renal function in a high-fat diet (HFD) induced NAFLD rat model. MATERIALS AND METHODS: Thirty-five male Wistar rats were randomly assigned to five groups (control, HFD, HFD + CAF, HFD + NAR, HFD + CAF + NAR; n = 7 per group). The HFD groups were fed a HFD (51% calories from fat) for 16 weeks, and from Week 10, received oral treatments with CAF (50 mg/kg/day), NAR (12.5 mg/kg/day), or their combination for 6 weeks. Key outcomes, including insulin resistance (HOMA-IR), renal function (BUN, creatinine, and eGFR), and systemic inflammation (hs-CRP) were evaluated at the study's conclusion. FINDINGS: HFD significantly increased glucose, HOMA-IR, BUN, and hs-CRP (p < 0.0001), as well as insulin and creatinine levels (p < 0.001), whereas eGFR decreased (p < 0.01) compared with controls. Treatment with CAF or NAR partially improved these parameters. The combination therapy produced the most pronounced effects, significantly lowering HOMA-IR and creatinine (p < 0.0001), BUN and glucose (p < 0.001), insulin (p <0.01), and hs-CRP levels (p <0.05), while increasing eGFR (p < 0.01). CONCLUSION: The CAF-NAR combination demonstrated superior effects compared with monotherapies in the NAFLD rat model, improving insulin resistance, enhancing renal function, and reducing systemic inflammation, thereby highlighting its potential as a promising approach for managing NAFLD-related metabolic and renal complications.