While these results do provide a deeper understanding of the role Nrf2 and NF‐κB play in hyperlipidemia‐induced cardiac injury and provide support for targeting the Nrf2 and NF‐κB pathways in the treatment of obesity‐related complications, more information is needed to clarify the mechanism behind X22′s cardioprotective effects. Here, NFKB1 is linked to obesity due to melanocortin 4 receptor deficiency.