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Author ORCID Identifier

https://orcid.org/0000-0002-2722-507X

Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Food Science

Year Degree Awarded

2019

Month Degree Awarded

September

First Advisor

Professor Guodong Zhang

Second Advisor

Professor Hang Xiao

Third Advisor

Professor 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.

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