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

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ID: 13027
2018
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Abstract
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 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 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.
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li2018transcriptomecell Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Li, Ruifang;Grimm, Sara A.;Mav, Deepak;Gu, Haiwei;Djukovic, Danijel;Shah, Ruchir;Merrick, B. Alex;Raftery, Daniel;Wade, Paul A.;
Journal Cell reports
Year 2018
DOI
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URL
http://www.sciencedirect.com/science/article/pii/S2211124717319083
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