Exercise training and enalapril mitigate steatotic liver disease and islet disarrangement but diverge in inflammatory modulation in obese mice.

Metabolic-associated steatotic liver disease (MASLD) is increasingly prevalent worldwide. We previously demonstrated that enalapril and aerobic exercise training (AET) improve steatosis in an obesity model. Here, we investigated the effects of both interventions on pancreatic morphology, oxidative stress, and inflammatory cytokines in the steatotic liver. Male C57BL/6 mice were fed either a standard chow (SC) or a high-fat diet (HF) for 8 weeks. The HF group was divided into enalapril treatment (HF-E, 10 mg/kg/day), AET (HF-T, 300 min/week treadmill running), and both interventions (HF-ET) for 8 additional weeks alongside the HF diet. We measured body mass (BM) gain, plasma cytokines, and pancreatic islet structure. Liver mass, oxidative stress, renin-angiotensin system (RAS), and cytokines were also evaluated. The HF group showed greater BM gain, higher pro-inflammatory cytokines, and hypertrophied pancreatic islets than the SC group. All interventions reduced these parameters, though the HF-E group maintained an enlarged pancreatic islet. In the liver, all interventions improved oxidative stress and reduced RAS overactivation. However, enalapril-treated groups retained elevated IL-6, NFκB, TGF-β, and CD11c protein levels, whereas trained groups exhibited levels comparable to SC. In conclusion, both interventions improved islet structure, oxidative stress, and RAS overactivation, but enalapril failed to reverse the pro-inflammatory cytokine profile in obese mice.