In humans, many DEGs at obesity persist at 2 yr post-WL—especially in adipocytes/APCs/endothelium—with metabolic genes (e.g., IGF1, LPIN1, IDH1) remaining downregulated and fibrosis/apoptosis/TGFβ programs up. In mice, adipocyte promoters/enhancers retain memory (persistent H3K4me3/H3K27ac at inflammatory/ECM genes such as ICAM1, LYZ2, TYROBP; repressive H3K27me3 at adipogenesis/identity genes such as GPAM, ACACB, CYP2E1); LAM enrichment not fully normalized. The gene discussed is CYP2E1; the disease is obesity due to melanocortin 4 receptor deficiency.