We found that accumulation of lipids in primary rat hepatocytes induces hypermethylation of the OTC promotor gene and eventually a decrease in the gene expression of OTC. These observations were extended by in vivo studies demonstrating hypermethylation of the promoter region of OTC in rats and of both the CPS1 and OTC genes in patients with NAFLD, which in fact overlapped with hypermethylated regions in the OTC gene in rats.19 The gene discussed is OTC; the disease is metabolic dysfunction-associated steatotic liver disease.