Dihydromyricetin stimulates irisin secretion partially via the PGC-1α pathway

Irisin, derived from FNDC5, is an exercise-induced myokine that can stimulate the 'browning' of white adipose tissue, which is regulated by peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α). Dihydromyricetin (DHM), a natural flavonoid, exerts its activities through PGC-1α activation. Here, we explored whether DHM could mimic the effects of exercise on irisin secretion. DHM administration increased circulating irisin in rats and humans. Notably, the serum irisin level had a greater correlation to the level of circulating DHM than to the amount of exercise. DHM treatment upregulated PGC-1α and FNDC5 expression, enhanced energy metabolism, as evidenced by NMR-based metabonomics analysis, and partially abolished the suppressive effects of Pgc-1α siRNA on FNDC5 expression. These results suggest that DHM can stimulate irisin secretion partially via the PGC-1α pathway. As a potent exercise mimetic, DHM is expected to benefit patients suffering from metabolic diseases, especially those who cannot undergo rigorous exercise.