الفهرس 
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Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a major health concern globally because of its high frequency, challenges in diagnosis, complexity of pathophysiology, and lack of FDA approved pharmacotherapy. Vitamin D3 (VD3) has anti-steatosis, anti-inflammatory, insulin sensitizing and anti-fibrotic roles; hence, it holds promise to impede certain liver conditions, including MAFLD, by impeding the progression of the disease. MicroRNA-34a (miR-34a) was previously found in many studies to play a critical role in the pathogenesis of fatty liver and disease progression. However, the extent of vitamin D3’s protective effects on MAFLD through the modulation of miR-34a has not been investigated.
The aim of this work was to study the effects of different doses of oral Vitamin D3 supplementation on main features of MAFLD including obesity, dyslipidemia, insulin resistance, hepatic steatosis, and inflammation in an experimental model of male albino rats with high-fat diet (HFD)-induced MAFLD, in comparison to a control group.
A group of 50 male albino rats was randomly divided into control and MAFLD groups, with the MAFLD group being fed a HFD for the duration of 14 weeks. The MAFLD group was further subdivided into three vitamin D3-treated groups at different doses and one untreated group. After the study period, the serum and liver tissue was used for the determination of relative miR-34a expression by real-time quantitative PCR (RT-qPCR), as well as for histological and biochemical analysis.
When compared to the control group, a HFD caused significant liver steatosis, inflammation, ballooning, increased body and liver weight, liver index, dyslipidemia, hyperglycemia, insulin resistance, elevated serum ALT and significant overexpression of miR-34a in serum and hepatic tissue (P< 0.0001). Also, Vitamin D3 supplementation in conjunction with a HFD demonstrated, in a dose dependent manner, its efficacy in improving morphological changes in liver tissues. Vitamin D3 significantly reduced the relative expression of miR-34a in serum and liver tissue compared to the untreated group fed a HFD (P< 0.0001).
In conclusion, Vitamin D3 supplementation has been found in this study to improve MAFLD associated dyslipidemia, hyperglycemia, insulin resistance, steatosis and inflammation, and hence prevent disease progression. Additionally, miR-34a shows a promise as a prognostic biomarker for MAFLD progression and treatment success.