Figure 1.

The physiological role of miR-22 in metabolism. miR-22 is a metabolic regulator that mediates the transcriptional silencing of key genes involved in gluconeogenesis, lipogenesis, fatty acid oxidation (FAO), and the beiging of white adipose tissue (WAT). Hepatic glucose production is induced in the liver under the influence of thyroid hormones such as 3,5-diiodo-L-thyronine (T2), possibly through the direct activation of SIRT1 and inhibition of miR-22, further inducing the expression of PEPCK and G6Pase via PGC-1α and TCF7 increases. miR-22 also inhibits the peroxisomal and mitochondrial β oxidation directly targeting PPAR-α, which induces the secretion of FGF21 to control the expression of PPARGC1A in a paracrine and endocrine manner, respectively, in WAT. Here, the activation of PGC-1α through SIRT1 modulates TFAM and UCP1, increasing mitochondrial biogenesis and energy expenditure, respectively, cell programs characteristic of the more metabolically active brown adipose tissue. In skeletal muscle, miR-22 is responsible for the inhibition of lipid catabolism via estrogen receptor alpha (ER- α) and for promoting anabolic pathways via mTOR derepression. miR-22 also controls muscle fiber switch, favoring fast-twitching glycolytic fibers, and it can be released in the bloodstream within extracellular vesicles (EVs) to post-transcriptionally control the expression of its targets in distal organs. This figure was based on BioRender templates.