NAFLD and Vitamin D: Evidence for Intersection of MicroRNA Regulated Pathways

Non-alcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease, worldwide. The molecular pathogenesis of NAFLD is complex, involving numerous signalling molecules including microRNAs (miRNAs). Dysregulation of miRNA expression is associated with hepatic inflammation, fibrosis and hepatocellular carcinoma. Although miRNAs are also critical to the cellular response to vitamin D, mediating regulation of the vitamin D receptor (VDR) and vitamin D’s anticancer effects, a role for vitamin D regulated miRNAs in NAFLD pathogenesis has been relatively unexplored. Therefore, this review aimed to critically assess the evidence for a potential subset of miRNAs that are both dysregulated in NAFLD and modulated by vitamin D. Comprehensive review of 89 human studies identified 25 miRNAs found dysregulated in more than one NAFLD study. In contrast, only 17 studies, including a protocol for a trial in NAFLD, had examined miRNAs in relation to vitamin D status, response to supplementation, or vitamin D in the context of the liver. This paper summarises these data and reviews the biological roles of six miRNAs (miR-21, miR-30, miR-34, miR-122, miR-146, miR-200) found dysregulated in multiple independent NAFLD studies. While modulation of miRNAs by vitamin D has been understudied, integrating the data suggests seven vitamin D modulated miRNAs (miR-27, miR-125, miR-155, miR-192, miR-223, miR-375, miR-378) potentially relevant to NAFLD pathogenesis. Our summary tables provide a significant resource to underpin future hypothesis-driven research, and we conclude that the measurement of serum and hepatic miRNAs in response to vitamin D supplementation in larger trials is warranted.