found that supplementation of irisin in Ang II–treated cardiomyocytes significantly increased the expression of LC3II and decreased P62 expression and activated the phosphorylation of AMPK (Thr172) and ULK1 (Ser555), thereby reducing cardiomyocyte apoptosis, and this protection will be reversed by autophagy inhibitor such as 3-methyladenine, autophagy-related 5 siRNA (ATG5), and chloroquine; moreover, blockage of AMPK and ULK1 also abrogated autophagy flux and indicted irisin-induced protective autophagy in cardiac hypertrophy via activating AMPK-ULK1 pathway (120, 121). The gene discussed is ATG5; the disease is cardiac hypertrophy.