Beneficial Effect of Vitamin D on Non-Alcoholic Fatty Liver Disease (NAFLD) Progression in the Zebrafish Model

Abstract

A major cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma, non-alcoholic fatty liver disease (NAFLD) results from excessive liver fat accumulation. Vitamin D (VitD) plays multiple important roles in diverse physiologic processes. Here, we describe the role of VitD in the complex pathogenesis of NAFLD and explore the possible therapeutic role of VitD supplementation in NAFLD therapy. To compare the effect of VitD to other interventions such as low-calorie diet, we induced NAFLD in young adult zebrafish (Danio rerio, AB strain) and monitored the effects of VitD supplementation on the disease course. The zebrafish administered with high-dose VitD (1.25 μg) had significantly reduced liver fat compared to those that received low-dose VitD (0.049 μg) or caloric restriction. Gene expression analysis revealed that VitD downregulated several pathways that may play a role in NAFLD etiology, which affected fatty acid metabolism, vitamins and their cofactors, ethanol oxidation, and glycolysis. The pathway analysis revealed that the cholesterol biosynthesis pathway and the isoprenoid biosynthetic process pathway were significantly upregulated whereas the small molecule catabolic process pathway significantly downregulated following the exposure of NAFLD zebrafish model to high VitD dose. Therefore, our findings suggest the association of novel biochemical pathways with NAFLD and highlight the potential of VitD supplementation to reverse the severity of NAFLD, especially in younger people.

The Influence of Diet and Its Components on the Development and Prevention of Hepatocellular Carcinoma (HCC)

“…Aside from its impact on calcium–phosphorus metabolism and bone mineralization, Grinberg L. lists its anti-inflammatory, immune-system-regulating, fibrosis-inhibiting, and lipid-metabolism-regulating actions. Additionally, studies on animal models have demonstrated its ability to limit fat accumulation in the liver, which is noteworthy in preventing further consequences of the disease [ 49 ]. There are also reports of its anti-cancer properties [ 50 ].…”

β-Sitosterol Reduces the Content of Triglyceride and Cholesterol in a High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Zebrafish (Danio rerio) Model

“…The accumulation of lipid metabolites is closely associated with obesity or obesityrelated NAFLD [19]. NAFLD is often associated with metabolic syndrome features, such as dyslipidemia, hypertension, and T2DM [20]. The intrahepatic triglyceride accumulation (i.e., steatosis, the hallmark feature of NAFLD) results from an imbalance between complex molecular pathways of lipid metabolism [20].…”

“…NAFLD is often associated with metabolic syndrome features, such as dyslipidemia, hypertension, and T2DM [20]. The intrahepatic triglyceride accumulation (i.e., steatosis, the hallmark feature of NAFLD) results from an imbalance between complex molecular pathways of lipid metabolism [20]. Animal models are critical tools for studying NAFLD, as well as the development of therapeutic drugs and prevention and treatment strategies [20].…”

“…The intrahepatic triglyceride accumulation (i.e., steatosis, the hallmark feature of NAFLD) results from an imbalance between complex molecular pathways of lipid metabolism [20]. Animal models are critical tools for studying NAFLD, as well as the development of therapeutic drugs and prevention and treatment strategies [20]. There are several studies on NAFLD model organisms, such as rats [15], mice [21], and zebrafish [22].…”

“…NAFLD is a metabolic disorder with multiple causes, long-term hyperglycemia causes macrovascular or microvascular complications, such as retinopathy [28]. Meanwhile, a zebrafish model of HFD-induced NAFLD has achieved good application progress [20]. Therefore, in a diet-induced zebrafish model of NAFLD, the establishment of the model can be judged by examining the changes in body indicators, such as lipid changes [24], genetic changes [29], retinal vascular changes [28], etc.…”