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.
Aboudeya, H., Othman, H., & Mohasseb, M. (2025). 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, 45(4), 487-501. doi: 10.21608/besps.2025.368648.1206
MLA
Hebatallah Mohammed Aboudeya; Hala Othman; Magda Mohasseb. "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, 45, 4, 2025, 487-501. doi: 10.21608/besps.2025.368648.1206
HARVARD
Aboudeya, H., Othman, H., Mohasseb, M. (2025). '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, 45(4), pp. 487-501. doi: 10.21608/besps.2025.368648.1206
VANCOUVER
Aboudeya, H., Othman, H., Mohasseb, M. 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, 2025; 45(4): 487-501. doi: 10.21608/besps.2025.368648.1206
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