Identification of Genes in the Colon Tissue Associated with Serum Leptin and Insulin in Diet‐Induced Obese Mice

Abstract

Obesity‐induced chronic inflammation has been known to increase the risk of ulcerative colitis, Crohn's disease, and colorectal cancer. Accumulating evidence suggest that obesity‐associated phenotypes including leptin and insulin are key molecules linking obesity and diseases of the lower intestine. We identified serum phenotype‐associated genes in colon tissue of diet‐induced obese mice to interrogate candidate genes as early biomarkers of obesity‐associated colonic diseases. C57BL/6J mice were assigned to either normal diet (ND, 15% of fat calories) or high‐fat diet (HFD, 45% of fat calories) group for 8 weeks. Genome‐wide gene expression profiles of colon tissue were determined using Illumina MouseWG‐6 v2 Expression BeadChip, followed by statistical analyses to detect differentially expressed and to identify serum phenotype‐associated genes. Among differentially expressed genes affected by HFD, 135, 128, 110, and 341 genes were associated with serum concentration of leptin, insulin, IGF‐1, and adiponectin, respectively. We found 17 and 4 differentially expressed genes exhibited inverse relationships with serum leptin and serum insulin, respectively, by two different dietary types. Among these genes, leptin‐associated Peli3 (pellino E3 ubiquitin protein ligase family member 3), Creb1 (cAMP responsive element binding protein 1), and Enpp2 (ectonucleotide pyrophosphatase/phosphodiesterase 2, autotaxin) and insulin‐associated Centg1 (AGAP2, ArfGAP with GTPase domain) have been reported to play a role either in obesity or in colonic diseases. In conclusion, our data suggest that Peli3, Creb1, Enpp2, and Centg1 would be potential candidate early biomarkers of obesity‐induced pathophysiological changes in the colon. Further studies on gene functions related to diseases of lower intestine needs to be fulfilled.Support or Funding InformationThis research was supported by the SRC program (Center for Food & Nutritional Genomics: 2015R1A5A6001906) of the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology.