Further animal experiments showed that irisin treatment significantly alleviates endothelial dysfunction in diabetic mice and downregulates mRNA expression of macrophages and T lymphocytes in atherosclerotic plaques as well as expression of inflammatory cytokines (IL-6, TNF-α) in aortic tissue, which further abrogates development of atherosclerosis, and analysis showed that these anti-inflammatory effects are correlated with activation of the AMPK/PI3K/PKB/eNOS pathway by irisin (Lu et al., 2015). This evidence concerns the gene FNDC5 and atherosclerosis.