Transcriptome and DNA Methylome Analysis in a Mouse Model of Diet-Induced Obesity Predicts Increased Risk of Colorectal Cancer

Transcriptome and DNA Methylome Analysis in a Mouse Model of Diet-Induced Obesity Predicts Increased Risk of Colorectal Cancer

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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 a major risk, yet the mechanistic underpinnings remain poorly understood.Using a diet-induced obesity mouse model, we identified obesity-associated molecular changes Can Cooler 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 Concealers 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 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.