The protective effect of vitamin D against HFD-induced NAFLD through modulation of AMPK/fetuin-A/mTOR signaling pathway in male rats | ||
| Bulletin of Egyptian Society for Physiological Sciences | ||
| Volume 45, Issue 4, October 2025, Pages 487-501 PDF (486.17 K) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/besps.2025.368648.1206 | ||
| Authors | ||
| Hebatallah Mohammed Aboudeya* ; Hala Othman; Magda Mohasseb | ||
| Human Physiology Department, Medical Research Institute, Alexandria University, Egypt | ||
| Abstract | ||
| Vitamin D has attracted increasing attention as a therapeutic approach for NAFLD. However, the underlying mechanisms remain poorly understood. The present study aimed to investigate the effect of Vit D on NAFLD and the role of hepatic AMPK/fetuin-A/mTOR pathway in mediating this effect. Forty adult male Wistar rats were equally divided into four groups: control, Vit D, HFD, and HFD+Vit D. Rats were either fed with HFD or standard diet for 12 weeks. Vit D (5 μg/kg b.w. 1,25(OH)2D3) was given twice a week from the 5th week for 8 weeks. The present findings revealed significantly lower 25-hydroxyvitamin D serum levels with a significant decrease in hepatic VDR expression in the HFD-fed rats. Liver enzymes, fasting glucose, insulin, insulin resistance, triglycerides, total cholesterol, LDL-C and intrahepatic fat content were all significantly reduced, whereas HDL-C were significantly increased. This was reversed by Vit D treatment. Vit D significantly decreased serum fetuin-A, downregulated its hepatic expression in HFD-fed rats. This was accompanied by increased hepatic p-AMPK levels, decreased mTOR and SREBP-1c expression and protein levels. Vit D levels were negatively correlated with final body weight, HOMA-IR, hepatic TG, hepatic cholesterol and hepatic fetuin-A expression in HFD and HFD+Vit D groups. Hepatic fetuin-A expression was negatively correlated with p-AMPK and positively correlated with mTOR and SREBP-1c expression and protein levels. In Conclusion, vitamin D could ameliorate NAFLD via modulation of AMPK/fetuin-A/mTOR pathway, leading to suppression of SREBP-1c expression. This provides a novel perspective on the nutritional therapy for NAFLD. | ||
| Keywords | ||
| NAFLD; 1; 25(OH)2D3; AMPK/fetuin-A/mTOR | ||
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