The Effect of Aerobic Exercise and Resveratrol on Endoplasmic Reticulum Stress in Heart Tissue of NAFLD Rats with HFD

Background: Non-alcoholic fatty liver disease (NAFLD) is closely linked to extrahepatic complications, including cardiac dysfunction. Endoplasmic reticulum stress (ERS) is implicated in NAFLD progression, but its role in associated cardiac pathology remains understudied. This study evaluated the combined effects of aerobic exercise and resveratrol (RSV) on cardiac ERS markers (GRP78, CHOP) in NAFLD rats induced by a high-fat diet (HFD). Methods: Forty male Wistar rats (159.95 ± 19.70 g) were divided into five groups: healthy control (CON), NAFLD model (HFD), HFD + exercise (EX), HFD + RSV, and HFD + EX + RSV. RSV (20 mg/kg/day) was administered orally, while aerobic exercise involved treadmill running (15–20 m/min, 5 days/week) for 8 weeks. Results: HFD-induced NAFLD significantly increased GRP78 and CHOP expression vs. CON (p < 0.001). Both EX (GRP78: p = 0.014; CHOP: p = 0.046) and RSV (GRP78: p = 0.015; CHOP: p = 0.042) reduced these markers compared to HFD. The EX + RSV combination showed greater efficacy, lowering GRP78 and CHOP vs. HFD (p < 0.001), EX (GRP78: p = 0.039; CHOP: p = 0.038), and RSV (GRP78: p = 0.038; CHOP: p = 0.041). Conclusion: Aerobic exercise and RSV independently ameliorate cardiac ERS in NAFLD, but their synergistic effect yields superior outcomes. This highlights the potential of lifestyle-pharmacological interventions for NAFLD-related cardiac complications.