MicroRNAs in fatty liver disease

Overweight and obesity, insulin resistance and diabetes, chronic alcoholism, as well as infection by specific genotypes of hepatitis C viruses are all associated with an excessive and chronic ectopic accumulation of fat in the liver (steatosis). If the underlining causes of steatosis development are not resolved, progression toward more severe liver diseases such as inflammation, fibrosis, and cirrhosis can then occur with time. These hepatic metabolic and histological disorders are commonly referred to as fatty liver disease (FLD) and result from multiple deregulated molecular mechanisms controlling hepatic homeostasis. Among these mechanisms, deregulation of a whole network of small noncoding RNAs called microRNAs (miRNAs), which regulate gene expression at a posttranscriptional level, critically contributes to the development and progression of FLD. Specific miRNAs secreted in body fluids are also emerging as useful biomarkers of FLD and therapeutic targeting of miRNAs is currently being evaluated. The authors discuss recent findings highlighting the role and complexity of miRNA regulatory networks, which critically contribute to the development of FLD. As well, the potential therapeutic perspectives for FLD that our understanding of hepatic miRNA biology offers is considered.