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

Abstract

Metabolic syndrome (MetS) results from the cluster of several risk factors, including central obesity, insulin resistance, dyslipidemia, and hypertension. Around 20%–25% of the world’s adult population is estimated to have MetS (1). MetS has been estimated to confer a fivefold increase in the risk of type 2 diabetes (T2D) over the next 5–10 years (2). Both MetS and T2D increase the risk of cardiovascular disease (CVD) (3). MetS diagnosis is cumbersome. A simple noninvasive and inexpensive test that risk stratifies the general population before MetS onset would allow for primary prevention strategies, especially aggressive lifestyle modifications, and the more stringent monitoring of those individuals positive to the predictor. This may have an enormous impact on our national health systems, ultimately slowing down the diabetes epidemics. MicroRNAs (miRNAs, or miRs) are small noncoding RNA regulatory molecules that inhibit the expression of a plethora of mRNAs, which they target within their parent cells but also in other cells that they reach via different shuttling mechanisms (4). Such shuttles, including lipoproteins and extracellular vesicles, protect their cargos from degradation and deliver active miRNAs from cells to cells contributing to cell-to-cell communication. Moreover, by conferring resilience to miRNAs, the shuttles incidentally increase our possibilities to develop miRNAs in extracellular biomarkers. Among many different actions, miRNAs are now recognized as regulators of lipid and glucose metabolism and as involved in the development of metabolic and cardiovascular diseases (5,6). The liver-enriched miR-122 (now identified as miR-122-5p) was the first miRNA to be recognized functionally associated with a metabolic phenotype, and in particularly to regulate …