Abstract
BackgroundObesity 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.MethodsC57BL/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 log2 fold change of ≥1 or ≤−1 (twofold change), based on time-dependent expression patterns, followed by virtual network analysis.ResultsHigh-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, included Apoa4 (apolipoprotein A-IV), Ppap2b (phosphatidic acid phosphatase type 2B), Cel (carboxyl ester lipase), and Clps (colipase, pancreatic), which interacted strongly with surrounding genes associated with colorectal cancer or obesity.ConclusionsOur data indicate that Apoa4, Ppap2b, Cel, and Clps are 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12263-016-0547-x) contains supplementary material, which is available to authorized users.
Highlights
Obesity is known to increase the risk of colorectal cancer
Increased circulating concentrations of insulin and leptin are linked to abnormal hyperproliferation of colorectal tissue and inflammation possibly by controlling transcription factors involved in the expression of cell growth-regulating molecules [7,8,9,10,11,12]
At the end of 12 weeks, high-fat diet (HFD)-fed mice gained 22.3 g weight compared with Normal diet (ND)-fed mice that gained 15.3 g weight (P < 0.001)
Summary
Obesity is known to increase the risk of colorectal cancer. 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. Epidemiological evidence indicates that excess body fat is associated with an increased risk of colorectal cancer (CRC) [3]. Experimental studies indicate that diet-induced obesity causes pathological changes in the colon. Increased circulating concentrations of insulin and leptin are linked to abnormal hyperproliferation of colorectal tissue and inflammation possibly by controlling transcription factors involved in the expression of cell growth-regulating molecules [7,8,9,10,11,12]. To our knowledge, no study has identified candidate molecules involved in obesityassociated pathological changes in the colon of HFD-fed mice. Limited information is available on mechanisms underlying the pathophysiological changes in the colon tissue of obese animals
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