miRNA Dysregulation in the Development of Non-Alcoholic Fatty Liver Disease and the Related Disorders Type 2 Diabetes Mellitus and Cardiovascular Disease

Abstract

According to the World Health Organization, the continuing surge in obesity pandemic creates a substantial increase in incidences of metabolic disorders, such as non-alcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus, and cardiovascular disease. MicroRNAs (miRNAs) belong to an evolutionarily conserved class of short (20-22 nucleotides in length) and single-stranded non-coding RNAs. In mammals, miRNAs function as critical post-transcriptional negative regulators involved not only in many biological processes but also in the development of many diseases such as NAFLD and comorbidities. More recently, it has been described that cells can secrete miRNAs in extracellular vesicles, transported by body fluids, and uptaken by other tissues regulating gene expression. Therefore, this could be a mechanism of signaling involved not only in physiological pathways but also in the development of diseases. The association of some miRNA expression profiles with certain disorders has made them very interesting molecules for diagnosis, prognosis, and disease management. The finding of specific miRNA signatures to diagnose NAFLD and related diseases could anticipate the risk of development of related complications and, actually, it is the driving force of present health strategies worldwide. In this review, we have included latest advances in knowledge about the miRNAs involved in the development of NAFLD and related diseases and examined how this knowledge could be used to identify new non-invasive biomarkers and new pharmacological interventions.

Recent Update on the Molecular Mechanisms of Gonadal Steroids Action in Adipose Tissue

“…Knowledge on the role of miRNAs in the regulation of metabolism and development of metabolic diseases is developing intensively [ 276 ]. The role of miRNAs in the development of metabolic diseases such as obesity, T2D, polycystic ovary syndrome, nonalcoholic fatty disease, cardiovascular and inflammatory diseases was recently reviewed [ 277 , 278 , 279 , 280 , 281 , 282 , 283 ]. Moreover, the expression of aquaporin isoforms associated with metabolic diseases is also regulated by microRNAs [ 284 ].…”

“…Moreover, the expression of aquaporin isoforms associated with metabolic diseases is also regulated by microRNAs [ 284 ]. Studies describing the regulation of microRNAs expression by gonadal steroids [ 34 , 35 , 36 , 37 ] and the association of microRNAs with metabolic diseases [ 277 , 278 , 279 , 280 , 281 , 283 , 284 , 285 ], allowed to identify the most important microRNAs in metabolic diseases which expression level may be regulated by sex hormones ( Table 2 ).…”

Non-Coding RNAs: Novel Players in Insulin Resistance and Related Diseases

“…NAFLD is the most common liver disease in western countries [ 21 ]. Prevalence of NAFLD is rising in parallel to a worldwide increase in diabetes and MetS [ 22 , 23 ], and it is estimated to occur in up to 45% of the general population—but is even doubled in individuals with MetS [ 13 ]. The strong association of NAFLD with obesity and T2D is mainly attributable to IR, leading to visceral adiposity and lipid accumulation in the liver [ 20 ].…”

“…Progression from steatosis to NASH is driven by different mechanisms, including lipotoxicity, oxidative stress and immune system activation. Even though extensively studied, the molecular mechanisms involved in steatosis development, as well as the pathways leading to progressive hepatocellular damage following lipid accumulation, are still poorly understood [ 23 , 26 , 27 ].…”

Extracellular Vesicles-Mediated Transfer of miRNA Let-7b from PC3 Cells to Macrophages

“…Regulation of gene expression by miRNA molecules is a conventional function of these biomolecules; for example, miRNAs exert a modulatory effect of several inflammatory signaling pathways [ 11 ]. To this respect, aberrant miRNA Let-7 expression has been associated with a variety of human diseases such as cardiovascular diseases, cystic fibrosis, metabolic disease as type 2 diabetes mellitus and cancer [ 12 , 13 , 14 , 15 , 16 ]. The Let-7 gene encodes a highly conserved miRNA family, whose members have generally thought to be overlapping because of sequence similarity [ 15 , 16 ].…”