Blood hsa-miR-122-5p and hsa-miR-885-5p levels associate with fatty liver and related lipoprotein metabolism—The Young Finns Study

Abstract

MicroRNAs are involved in disease development and may be utilized as biomarkers. We investigated the association of blood miRNA levels and a) fatty liver (FL), b) lipoprotein and lipid pathways involved in liver lipid accumulation and c) levels of predicted mRNA targets in general population based cohort. Blood microRNA profiling (TaqMan OpenArray), genome-wide gene expression arrays and nuclear magnetic resonance metabolomics were performed for Young Finns Study participants aged 34–49 years (n = 871). Liver fat status was assessed ultrasonographically. Levels of hsa-miR-122-5p and -885-5p were up-regulated in individuals with FL (fold change (FC) = 1.55, p = 1.36 * 10−14 and FC = 1.25, p = 4.86 * 10−4, respectively). In regression model adjusted with age, sex and BMI, hsa-miR-122-5p and -885-5p predicted FL (OR = 2.07, p = 1.29 * 10−8 and OR = 1.41, p = 0.002, respectively). Together hsa-miR-122-5p and -885-5p slightly improved the detection of FL beyond established risk factors. These miRNAs may be associated with FL formation through the regulation of lipoprotein metabolism as hsa-miR-122-5p levels associated with small VLDL, IDL, and large LDL lipoprotein subclass components, while hsa-miR-885-5p levels associated inversely with XL HDL cholesterol levels. Hsa-miR-885-5p levels correlated inversely with oxysterol-binding protein 2 (OSBPL2) expression (r = −0.143, p = 1.00 * 10−4) and suppressing the expression of this lipid receptor and sterol transporter could link hsa-miR-885-5p with HDL cholesterol levels.

Circulating MicroRNAs to Predict the Risk for Metabolic Diseases in the General Population?

“…In particular, once validated, circulating miR-122 appears to be a promising functional biomarker, able to sense changes in hepatic metabolism as well as to induce them. In support of this hypothesis, an association of miR-122-5p with fatty liver and related lipoprotein metabolism was recently described in a Finnish general population cohort (15). This reinforces the concept that increased circulating miR-122 might flag a problem with liver metabolisms and require further laboratory and clinical analyses going beyond the normal routine.…”

Bariatric Surgery Alters microRNA Content of Circulating Exosomes in Patients with Obesity

“…We found that exosomal miR‐122‐5p is associated with obesity. Circulating miR‐122‐5p is associated with fatty liver and lipoprotein metabolism and is being considered as a marker for acute myocardial infarction . Antagonizing miR‐122 levels in vivo decreases cholesterol levels and increases hepatic fatty acid oxidation .…”

Cell-Free Circulating Nucleic Acids as Early Biomarkers for NAFLD and NAFLD-Associated Disorders

“…Multiple previous studies have been focused on discriminating various NAFLD stages by analyzing miRNA expression profiles in liver parenchyma ( Guo et al, 2016 ; Soronen et al, 2016 ; Latorre et al, 2017 ). However, only several research groups have so far investigated NAFLD-associated changes in the spectrum of extracellular miRNAs present in human blood ( Cermelli et al, 2011 ; Yamada et al, 2013 ; Miyaaki et al, 2014 ; Tan et al, 2014 ; Becker et al, 2015 ; Pirola et al, 2015 ; Akuta et al, 2016 ; Liu et al, 2016 ; Raitoharju et al, 2016 ; Salvoza et al, 2016 ; Thompson et al, 2017 ) ( Table 1 ). These reports strongly suggest that circulating miRNAs can be utilized as more sensitive and specific biomarkers of liver damage as compared to currently employed biochemical tests based on measuring the relative activity of serum transaminases.…”

“… Raitoharju et al (2016) reported the association of blood miR-122 and miR-885 concentrations with ultrasonically assessed fatty liver in Finns study participants aged 34–49 years. As this study cohort was unusually large, the confidence of the reported findings was impressive; thus, Bonferroni-corrected p -values for miR-122 and miR-885 constituted 1.92 × 10 -15 and 2.58 × 10 -4 , respectively.…”

“…For the prediction of NAFLD, the levels of miR-122 were comparable in its performance to liver transaminases levels. However, combining miR-122 and miR-885 levels with common NAFLD risk factors improved the risk stratification only marginally; therefore, the authors were convinced against the clinical value of blood miRNA levels for the diagnostics of NAFLD in general population ( Raitoharju et al, 2016 ).…”