Figure 3.

miRNAs involved in cholesterol metabolism and NAFLD. Several miRNAs are involved in cholesterol metabolism and NAFLD, such as miR-122, miR-34a, miR-33 and miR-21. miR-122 is responsible for the regulation of SREBP-2 in its inactive form and is normally expressed at a high level in the liver, but in NAFLD patients, there seems to be a decrease in miR-122 expression level, which causes an increase in the transcription factor SREBP-2. miR-34a has a key role in the development of NAFLD through its involvement in the dysregulation of cholesterol metabolism. miR-34a is responsible for the suppression of sirtuin 1 (encoded by SIRT1), which in turn is responsible for regulating AMP kinase (AMPK) activity, which regulates HMGCR phosphorylation. When miR-34a levels increase, SIRT1 suppresses AMPK, which causes a decrease in HMGCR levels. As a result of this series of actions, the regulation of cholesterol metabolism is impaired, and there is an increase in cholesterol accumulation in the liver, which contributes to the development of NAFLD. miR-33 is overexpressed in the liver of NAFLD patients and functions as a regulator of lipid and insulin metabolism; when it is overexpressed, it suppresses ABCA1 expression. Suppression of ABCA1 results in a reduction in cholesterol efflux to ApoA-I, which is a key player in the regulation of reverse cholesterol transport. High levels of miR-21 also characterize NAFLD/NASH patients; a high level of miR-21 causes the accumulation of fats in the liver and leads to an increase in HMGCR expression and impaired regulation of cholesterol metabolism. (Created with BioRender.com (accessed on 1 September 2022)).