Analysis of miRNA Expression Profiles in High Cholesterol Diet-Induced MASH Progression: Potential Effect of α-Tocopherol

Abstract

Metabolic dysfunction-associated fatty liver disease (MAFLD), defined by fat accumulation in more than 5% of hepatocytes, is a common metabolic syndrome worldwide. However, 30%–40% of MAFLD cases progress to metabolic dysfunction-associated steatohepatitis (MASH), increasing the importance of the disease. MicroRNAs (miRNAs), non-coding RNA molecules approximately 21 nucleotides long, are used as biomarkers in many diseases and play a crucial role in regulating cellular processes by affecting gene expression. It is also known that miRNAs are effective in the progression of MASH and its profile depends on the stage of the disease. Therefore, we determined the relationship between MASH and miRNA profiles in an in vivo trial using an established model of cholesterol-induced MASH in rabbits. We also evaluated the impact of α-tocopherol, which is known to have a protective effect in MAFLD/MASH transition, on miRNA profiles. Regarding the limited information using rabbits, we first performed miRNA screening and identified miRNAs that are already described in rabbits or other organisms as well as the putative ones. Among those, two putative miRNAs (miR-230 and miR-1146) determined by sequencing may be important in the diagnosis and treatment of the disease. Furthermore, levels of five miRNAs (miR-122-5p, miR-199-5p, miR-145-5p, miR-27b-3p, miR-34a-5p) and their relevance in the pathogenesis of MASH were determined by RT-PCR and target gene prediction, respectively. In conclusion, the present study provides novel information regarding dysregulated miRNAs in high-cholesterol diet-induced MASH and the impact of α-tocopherol.