Poster Topical Area: Aging and Chronic Disease

Location: Auditorium

Poster Board Number: 122

P01-104 - Dietary intake of mildly oxidized fat increases colitis and colitis-associated colon tumorigenesis through activation of Toll-like receptor 4 (TLR4) signaling

Sunday, Jun 10
8:00 AM – 6:00 PM

Objectives: The incidence and prevalence of inflammatory bowel disease (IBD) in the US and other countries are increasing, making IBD a serious health problem. The rapid development suggests that environmental and dietary factors, rather than genetic drifts, could be primarily responsible for the growing incidences of IBD. It is important to identify these risk factors, in order to develop targeted strategies for prevention. In this study, we examined whether oxidized dietary fats, which are commonly found at high levels in a typical Western diet, are capable of exaggerating colonic inflammation and colon tumorigenesis.


Methods:
We purified commercial vegetable oil by silicic acid-activated charcoal chromatography to prepare un-oxidized oil, which was then oxidized in a well-controlled and well-characterized manner to prepare the oxidized oil. We then evaluated the effects of un-oxidized and oxidized vegetable oils on dextran sodium sulfate (DSS)- and IL-10 knockout-induced colitis, and azoxymethane (AOM)/DSS-induced colon tumorigenesis in mice, and studied the roles of Toll-like receptor 4 (TLR4) signaling involved.


Results:
Compared with un-oxidized vegetable oil, dietary administration of oxidized vegetable oil, even at low oxidative status (within the recommended industrial limit of the oxidative status of vegetable oil), increased DSS- and IL-10 knockout-induced colitis. Reduced colon lengths, enlarged spleen tissues, enhanced immune cell infiltration, expression of pro-inflammatory genes and crypt damage in colon were observed.Moreover, dietary administration of oxidized fat increased AOM/DSS-induced colitis-associated colon tumorigenesis, with increased tumor size and total tumor burden. Oxidized vegetable oil increased activation of TLR4 signaling in the systemic circulation, by disrupting intestinal barrier function and thus enhancing circulating levels of lipopolysaccharide (LPS) and bacteria, and the pro-colitis effect of oxidized vegetable oil was abolished inTlr4-/- mice.


Conclusion:
Oxidized vegetable oil, even at low oxidative status, could be a novel risk factor of IBD and associated colon cancer.




Funding Source: a new faculty start-up and Faculty Research Grant/Healey Endowment Grant (FRG/HEG) from the University of Massachusetts Amherst (to G.Z.)
USDA NIFA grants 2016-67017-24423 (to G.Z.)
USDA NIFA grants 2014-67017-21762 (to Z.L.)
USDA NIFA grants 2016-67021-25147 (to X.H.)
National Natural Science Foundation of China (NSFC) grants 81702832, 21705126, and 21775119

CoAuthors: Weicang Wang – University of Massachusetts Amherst; Haixia Yang – University of Massachusetts Amherst; Katherine Sanidad – University of Massachusetts Amherst; David Johnson Johnson – University of Massachusetts Amherst; E. Ilker Ozay – University of Massachusetts Amherst; Weipeng Qi – University of Massachusetts Amherst; Manami Ando – Tokyo University; Daeyoung Kim – University of Massachusetts Amherst; Lisa Minter – University of Massachusetts Amherst; Xinfeng Zhao – Northwest University; Xiaohui Zheng – Northwest University; Hang Xiao – University of Massachusetts Amherst; Yeonhwa Park – University of Massachusetts Amherst; Zhenhua Liu – University of Massachusetts Amherst; Eric Decker – University of Massachusetts Amherst; Guodong Zhang – University of Massachusetts Amherst

Yuxin Wang


University of Massachussets
Amherst, Massachusetts