Colon Transcriptomics Reveals Sex-Dependent Metabolic Signatures in Response to 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Treatment in C57BL/6N Mice
Diets high in red meats, particularly meats cooked at high temperature, increase the risk of colon cancer due to a production of heterocyclic aromatic amines (HAAs). Of the identified HAAs, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most mass abundant colon carcinogen in charred m...
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| Format: | Article |
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/18/6620 |
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| author | Jeong Hoon Pan Cara Cicalo Brandy Le Suwon Jeon Sangyub Kim Kyung A. Hwang Byungwhi Kong Jin Hyup Lee Jae Kyeom Kim |
| author_facet | Jeong Hoon Pan Cara Cicalo Brandy Le Suwon Jeon Sangyub Kim Kyung A. Hwang Byungwhi Kong Jin Hyup Lee Jae Kyeom Kim |
| author_sort | Jeong Hoon Pan |
| collection | DOAJ |
| description | Diets high in red meats, particularly meats cooked at high temperature, increase the risk of colon cancer due to a production of heterocyclic aromatic amines (HAAs). Of the identified HAAs, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most mass abundant colon carcinogen in charred meat or fish. Here, we comprehensively examined sex-dependent colon transcriptome signatures in response to PhIP treatment to identify biological discrepancies. Eight-week-old male and female C57BL/6N mice were intraperitoneally injected with PhIP (10 mg/kg of body weight) and colon tissues were harvested 24 h after PhIP injection, followed by colon transcriptomics analysis. A list of differentially expressed genes (DEGs) was utilized for computational bioinformatic analyses. Specifically, overrepresentation test using the Protein Analysis Through Evolutionary Relationships tool was carried out to annotate sex-dependent changes in transcriptome signatures after PhIP treatment. Additionally, the most significantly affected canonical pathways by PhIP treatment were predicted using the Ingenuity Pathway Analysis. As results, male and female mice presented different metabolic signatures in the colon transcriptome. In the male mice, oxidative phosphorylation in the mitochondrial respiratory chain was the pathway impacted the most; this might be due to a shortage of ATP for DNA repair. On the other hand, the female mice showed concurrent activation of lipolysis and adipogenesis. The present study provides the foundational information for future studies of PhIP effects on underlying sex-dependent mechanisms. |
| first_indexed | 2024-03-10T16:25:46Z |
| format | Article |
| id | doaj.art-beccf772ec54403392093c2e4dcb2ac6 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:25:46Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-beccf772ec54403392093c2e4dcb2ac62023-11-20T13:16:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012118662010.3390/ijms21186620Colon Transcriptomics Reveals Sex-Dependent Metabolic Signatures in Response to 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Treatment in C57BL/6N MiceJeong Hoon Pan0Cara Cicalo1Brandy Le2Suwon Jeon3Sangyub Kim4Kyung A. Hwang5Byungwhi Kong6Jin Hyup Lee7Jae Kyeom Kim8Department of Behavioral Health and Nutrition, College of Health Sciences, University of Delaware, Newark, DE 19716, USADepartment of Behavioral Health and Nutrition, College of Health Sciences, University of Delaware, Newark, DE 19716, USADepartment of Behavioral Health and Nutrition, College of Health Sciences, University of Delaware, Newark, DE 19716, USADepartment of Behavioral Health and Nutrition, College of Health Sciences, University of Delaware, Newark, DE 19716, USADepartment of Pharmacology, Penn State College of Medicine, Penn State University, Hershey, PA 17033, USADepartment of Agrofood Resources, National Institute of Agricultural Sciences, Rural Development Administration, Jeollabuk-do 55365, KoreaDepartment of Poultry Science, Dale Bumpers College of Agricultural, Food and Life Sciences, University of Arkansas, Fayetteville, AR 72701, USADepartment of Food and Biotechnology, College of Science & Technology, Korea University, Sejong 30019, KoreaDepartment of Behavioral Health and Nutrition, College of Health Sciences, University of Delaware, Newark, DE 19716, USADiets high in red meats, particularly meats cooked at high temperature, increase the risk of colon cancer due to a production of heterocyclic aromatic amines (HAAs). Of the identified HAAs, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most mass abundant colon carcinogen in charred meat or fish. Here, we comprehensively examined sex-dependent colon transcriptome signatures in response to PhIP treatment to identify biological discrepancies. Eight-week-old male and female C57BL/6N mice were intraperitoneally injected with PhIP (10 mg/kg of body weight) and colon tissues were harvested 24 h after PhIP injection, followed by colon transcriptomics analysis. A list of differentially expressed genes (DEGs) was utilized for computational bioinformatic analyses. Specifically, overrepresentation test using the Protein Analysis Through Evolutionary Relationships tool was carried out to annotate sex-dependent changes in transcriptome signatures after PhIP treatment. Additionally, the most significantly affected canonical pathways by PhIP treatment were predicted using the Ingenuity Pathway Analysis. As results, male and female mice presented different metabolic signatures in the colon transcriptome. In the male mice, oxidative phosphorylation in the mitochondrial respiratory chain was the pathway impacted the most; this might be due to a shortage of ATP for DNA repair. On the other hand, the female mice showed concurrent activation of lipolysis and adipogenesis. The present study provides the foundational information for future studies of PhIP effects on underlying sex-dependent mechanisms.https://www.mdpi.com/1422-0067/21/18/6620colonic transcriptomesex-based differencelipolysismitochondrial dysfunctionPhIP metabolism |
| spellingShingle | Jeong Hoon Pan Cara Cicalo Brandy Le Suwon Jeon Sangyub Kim Kyung A. Hwang Byungwhi Kong Jin Hyup Lee Jae Kyeom Kim Colon Transcriptomics Reveals Sex-Dependent Metabolic Signatures in Response to 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Treatment in C57BL/6N Mice International Journal of Molecular Sciences colonic transcriptome sex-based difference lipolysis mitochondrial dysfunction PhIP metabolism |
| title | Colon Transcriptomics Reveals Sex-Dependent Metabolic Signatures in Response to 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Treatment in C57BL/6N Mice |
| title_full | Colon Transcriptomics Reveals Sex-Dependent Metabolic Signatures in Response to 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Treatment in C57BL/6N Mice |
| title_fullStr | Colon Transcriptomics Reveals Sex-Dependent Metabolic Signatures in Response to 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Treatment in C57BL/6N Mice |
| title_full_unstemmed | Colon Transcriptomics Reveals Sex-Dependent Metabolic Signatures in Response to 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Treatment in C57BL/6N Mice |
| title_short | Colon Transcriptomics Reveals Sex-Dependent Metabolic Signatures in Response to 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Treatment in C57BL/6N Mice |
| title_sort | colon transcriptomics reveals sex dependent metabolic signatures in response to 2 amino 1 methyl 6 phenylimidazo 4 5 b pyridine treatment in c57bl 6n mice |
| topic | colonic transcriptome sex-based difference lipolysis mitochondrial dysfunction PhIP metabolism |
| url | https://www.mdpi.com/1422-0067/21/18/6620 |
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