title: Time-course microarray analysis for identifying candidate genes involved in obesity-associated pathological changes in the mouse colon.
abstract: BACKGROUND
  Obesity is known to increase the risk of colorectal cancer. However, mechanisms underlying the pathogenesis of obesity-induced colorectal cancer are not completely understood. The purposes of this study were to identify differentially expressed genes in the colon of mice with diet-induced obesity and to select candidate genes as early markers of obesity-associated abnormal cell growth in the colon.
  
  
  METHODS
  C57BL/6N mice were fed normal diet (11% fat energy) or high-fat diet (40% fat energy) and were euthanized at different time points. Genome-wide expression profiles of the colon were determined at 2, 4, 8, and 12 weeks. Cluster analysis was performed using expression data of genes showing log2fold change of ≥1 or ≤-1 (twofold change), based on time-dependent expression patterns, followed by virtual network analysis.
  
  
  RESULTS
  High-fat diet-fed mice showed significant increase in body weight and total visceral fat weight over 12 weeks. Time-course microarray analysis showed that 50, 47, 36, and 411 genes were differentially expressed at 2, 4, 8, and 12 weeks, respectively. Ten cluster profiles representing distinguishable patterns of genes differentially expressed over time were determined. Cluster 4, which consisted of genes showing the most significant alterations in expression in response to high-fat diet over 12 weeks, includedApoa4(apolipoprotein A-IV),Ppap2b(phosphatidic acid phosphatase type 2B),Cel(carboxyl ester lipase), andClps(colipase, pancreatic), which interacted strongly with surrounding genes associated with colorectal cancer or obesity.
  
  
  CONCLUSIONS
  Our data indicate thatApoa4,Ppap2b,Cel, andClpsare candidate early marker genes associated with obesity-related pathological changes in the colon. Genome-wide analyses performed in the present study provide new insights on selecting novel genes that may be associated with the development of diseases of the colon.
authors.affiliation: Division of Food Science and Culinary Arts, Shinhan University, Gyeonggi-do, Republic of Korea.
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Bae
authors.affiliation: Department of Food and Nutrition, Sookmyung Women's University, 100 Cheongpa-ro 47-gil, Yongsan-gu, Seoul Republic of Korea.
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Kim
authors.affiliation: Department of Food and Nutrition, Sookmyung Women's University, 100 Cheongpa-ro 47-gil, Yongsan-gu, Seoul Republic of Korea.
authors.forename: Seong Yeon
authors.initials: SY
authors.lastname: Hong
authors.affiliation: Department of Food and Nutrition, Yonsei University, Seoul, Republic of Korea.|Food and Nutritional Genomics Research Center, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Taesun
authors.initials: T
authors.lastname: Park
authors.affiliation: School of Life Science and Biotechnology, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Sang Gyu
authors.initials: SG
authors.lastname: Lee
authors.affiliation: Department of Food Science and Nutrition, Kyungpook National University, Daegu, Republic of Korea.|Food and Nutritional Genomics Research Center, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Myung-Sook
authors.initials: MS
authors.lastname: Choi
authors.affiliation: Department of Food and Nutrition, Sookmyung Women's University, 100 Cheongpa-ro 47-gil, Yongsan-gu, Seoul Republic of Korea.|Food and Nutritional Genomics Research Center, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Sung
keywords: Clustering; Colorectal cancer; Gene expression; Obesity; Time-course microarray analysis; Virtual network analysis