In vivo40 and in vitro41–43 studies have explored leptin's protective role against myocardial ischemia, where exogenous leptin supplementation activates PI3K/Akt, MAPK pathways, and JAK2/STAT3 signaling pathway, reducing mitochondrial permeability transition pore (MPTP) opening, restoring cardiac glucose metabolism, improving cardiac electrophysiological activity, and lowering the expression of pro-inflammatory genes40–45. This evidence concerns the gene LEP and myocardial ischemia.