In vitro leptin exposure enhanced CCL2 expression/secretion and increased KDM6A/KDM6B and EP300 transcription, highlighting how obesity‐driven epigenetic mechanisms, including leptin‐mediated pathways, disrupt ASC plasticity and perpetuate adipose tissue dysfunction, offering novel therapeutic targets for metabolic disease intervention. This evidence concerns the gene CCL2 and obesity due to melanocortin 4 receptor deficiency.