FIGURE 5.

Proposed mechanisms of the anti-hypertrophic effects of resveratrol. Resveratrol, either directly or indirectly, activates AMPK via LKB1 and inhibits Akt. This results in a reduction of p70S6K and eEF2 activities and the subsequent inhibition of protein synthesis. The reduced Akt activity relieves the suppression of GSK-3β activity, which may also contribute to the inhibition of NFAT-mediated transcription. AMPK activation by resveratrol appears to mediate a major component of the diminished NFAT transcriptional activity in the nucleus via inhibition of calcineurin and yet to be identified mechanism(s). Resveratrol treatment may also decrease NFAT-mediated transcription via pathways independently of AMPK and Akt. Together, all of these resveratrol-mediated effects contribute to the inhibition of cardiac myocyte hypertrophy.