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Author ORCID Identifier
AccessType
Open Access Dissertation
Document Type
dissertation
Degree Name
Doctor of Philosophy (PhD)
Degree Program
Food Science
Year Degree Awarded
2019
Month Degree Awarded
September
First Advisor
Guodong Zhang
Second Advisor
Hang Xiao
Third Advisor
Zhenhua Liu
Subject Categories
Digestive System Diseases | Food Chemistry | Lipids
Abstract
Colon cancer is a major public health issue: it is expected to have 140,250 new cases and 50,630 deaths during 2018, making colon cancer the third most common type of cancer and the second leading cause of cancer death in the United States. Obesity is associated with enhanced colonic inflammation, which is a major risk factor of colorectal cancer. Currently, more than 35% of adults and nearly 17% of children are obese. Considering the obesity and colon cancer epidemic in the United States, there is an urgent need to identify novel therapeutic targets for obesity and colon cancer. Here, using a LC-MS/MS-based lipidomics approach and disease mouse models, we found that: 1) CYP monooxygenase and its-derived fatty acid epoxides are decreased in adipose tissues in HFD-induced obese mice; 2) CYP monooxygenase and its-derived fatty acid epoxides are upregulated in AOM/DSS-induced colon cancer; pharmacological inhibition or genetic ablation of CYP monooxygenase attenuates AOM/DSS-induced colon cancer in mice; 3) Dietary feeding of ω-3 PUFAs-rich diets increased levels of CYP-derived EDPs in both plasma and MC38 colorectal tumor of the treated mice, systematic treatment with EDPs suppressed growth of MC38 colorectal tumor in mice. Together, these results support that previous unappreciated CYP lipid metabolism pathway plays a vital role in the development of obesity and colon cancer. Moreover, our study identifies the major enzymes and their metabolites in CYP lipid metabolism pathway as novel therapeutic targets for treating obesity and colon cancer.
DOI
https://doi.org/10.7275/14655356
Recommended Citation
Wang, Weicang, "CYTOCHROME P450 MONOOXYGENASE-MEDIATED LIPID METABOLISM IN OBESITY AND COLON TUMORIGENESIS" (2019). Doctoral Dissertations. 1778.
https://doi.org/10.7275/14655356
https://scholarworks.umass.edu/dissertations_2/1778