The new pathogenetic mechanisms of the development of nonalcoholic fatty liver disease combined with metabolic syndrome: focus on microRNAs

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the worldwide most common liver disease. The modern pathogenesis of NAFLD is associated with disorders in the regulation of cellular processes by the microRNAs at the post-transcriptional level, in particular, by miRNA-34a and miRNA-122. Objective — to study the levels of miRNA-34a, microRNA-122 expression to determine their role in the development and progression of NAFLD combined with metabolic syndrome. Materials and methods. The examinations involved 78 patients with NAFLD combined with components of metabolic syndrome. The control group consisted of 30 healthy donors, matched by age and sex. Patients’ examinations included general-clinical examination, laboratory tests (carbohydrate and lipid metabolism parameters), determination of the degree of liver steatosis by ultrasound, and evaluation of expression of miR‑34a and miR‑122 by fluorometric method. Results. The levels of circulating miRNA-34a and 122 in plasma samples of patients with NAFLD significantly exceeded the corresponding values in the control group. An elevated level of miRNA-34a and -122 may be a potential marker for the development of NAFLD. A significant association of the level of expression of miR‑34a with visceral adipose tissue and the index of insulin resistance was determined. The obtained data may indicate the possible effect of miRNA-34a on lipogenesis activation and disturbance of the distribution of adipose tissue. The role of miR‑122 in the lipid metabolism dysregulation toward the increase of fractions of proatherogenic lipoproteins involved in the formation of NAFLD is established. MicroRNA-122 may act 1as a non-invasive marker for the progression of fibrosis in patients with NAFLD with signs of metabolic syndrome. Conclusions. The increased miRNA-34a, miRNA-122 levels can serve as a potential marker of the NAFLD development. In NAFLD patients with the signs of metabolic syndrome, miRNA-122 can be used as a non-invasive marker of fibrosis progression.