Intermittent fasting alleviates high-fat-diet-induced fatty liver disease via TGF-β1 and MMP-9 regulation in albino rats

Fatty liver disease has become increasingly prevalent. While intermittent fasting (IF) is gaining popularity for its potential metabolic benefits, its specific effects on liver function and related molecular pathways remain unclear. This study aimed to examine the impact of IF on liver function, histological changes, and transforming growth factor-B1 (TGF-B1) and matrix metalloproteins 9 (MMP 9) hepatic expressions. A total of 24 male Sprague Dawley rats were divided into four groups: Control group, Lean fasting group fed standard chow combined with IF, Fatty liver group fed high-fat diet (HFD), Fasting fatty liver group fed HFD combined with IF as 24-h alternate-day fasting for eight weeks. Finally, oxidative stress, hepatic histology, immunohistochemistry expression of TGF-β and MMP 9, liver function tests, and m RNA expression of inflammatory markers were evaluated. The results showed that IF combination with HFD has decreased the degree of degenerative alterations and fibrosis at the portal area (p < 0.001), along with a considerable reduction in liver enzymes (p < 0.001), glucose and cholesterol (p < 0.001), oxidative stress, and inflammation caused by IF. Furthermore, compared to the fatty liver group, there was a significant decrease in hepatic expression of MMP 9 (p < 0.001), and TGF-β1 (p < 0.001). In our conclusion, by regulating TGF-β1 and MMP 9 expression in HFD-fed rats and having anti-inflammatory and antioxidative stress capabilities, IF may lessen hepatic fibrotic alterations.