Concerted regulation of non-alcoholic fatty liver disease progression by microRNAs in apolipoprotein E deficient mice.

Non-alcoholic fatty liver disease (NAFLD) prevalence is constantly increasing and microRNAs (miRNAs) altered expression fosters the development and progression of many pathologies, including NAFLD. Therefore, we explored the role of new miRNAs involved in the molecular mechanisms that trigger NAFLD progression and evaluated them as biomarkers for diagnosis. As a NAFLD model, we used apolipoprotein E deficient mice submitted to high fat diet during 8 or 18 weeks. After 18 weeks on diet, we demonstrate that insulin resistance and decreased lipogenesis and autophagy are related to a concerted regulation carried out by miR-26b-5p, miR-34a-5p, miR-149-5p and miR-375-3p. We also propose circulating let-7d-5p and miR-146b-5p as potential biomarkers of early stages of NAFLD. Finally, we confirmed that circulating miR-34a-5p and miR-375-3p are elevated in the late stages and miR-27b-3p and miR-122-5p are increased with disease progression. Our results reveal a synergistic regulation by miRNAs of key processes in NAFLD development and progression. Finally, we propose new biomarkers for NAFLD diagnosis. Notwithstanding, more efforts are needed to unravel the role of these miRNAs for developing new strategies for NAFLD treatment.