Colorectal cancer (CRC) tends to occur at older age; however, CRC incidence rates have been rising sharply among young age groups.The increasing prevalence of obesity is recognized as hyfrodol a major risk, yet the mechanistic underpinnings remain poorly understood.Using a diet-induced obesity mouse model, we identified obesity-associated molecular changes in the colonic epithelium of young and aged mice, and we further investigated whether the changes were reversed after weight loss.Transcriptome analysis indicated that obesity-related colonic cellular metabolic switch favoring long-chain fatty acid oxidation happened in young mice, while obesity-associated downregulation of negative feedback regulators of pro-proliferative signaling pathways occurred in older mice.Strikingly, colonic DNA methylome was pre-programmed by invertatop squeeze bottle obesity at young age, priming for a tumor-prone gene signature after aging.
Furthermore, obesity-related changes were substantially preserved after short-term weight loss, but they were largely reversed after long-term weight loss.We provided mechanistic insights into increased CRC risk in obesity.