Dihydromyricetin stimulates irisin secretion partially via the PGC-1α pathway. (5th September 2015) - Zhou, Qicheng
Highlights: DHM treatment significant increased serum Irisin levels in humans and rats. The serum irisin level had a greater correlation to the level of circulating DHM. DHM treatment upregulated PGC-1α and FNDC5 expression, enhanced energy metabolism by NMR-based metabonomics analysis. DHM partially abolished the suppressive effects of Pgc-1α siRNA on FNDC5 expression in skeletal muscle myotubes. DHM, as a potent exercise mimetic, is expected to benefit patients suffering from metabolic diseases. Abstract: 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.