Azoxymethane Alters the Plasma Metabolome to a Greater Extent in Mice Fed a High-Fat Diet Compared to an AIN-93 Diet
Consumption of a high-fat diet (HFD) links obesity to colon cancer in humans. Our data show that a HFD (45% energy fat versus 16% energy fat in an AIN-93 diet (AIN)) promotes azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) formation in a mouse cancer model. However, the underlying metab...
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doaj-5c08041df51e4c88ab4ff084b4f44f012021-07-23T13:53:46ZengMDPI AGMetabolites2218-19892021-07-011144844810.3390/metabo11070448Azoxymethane Alters the Plasma Metabolome to a Greater Extent in Mice Fed a High-Fat Diet Compared to an AIN-93 DietHuawei Zeng0Shahid Umar1Zhenhua Liu2Michael R. Bukowski3Grand Forks Human Nutrition Research Center, Agricultural Research Service, United States Department of Agriculture, Grand Forks, ND 58203, USADepartment of Surgery and University of Kansas Cancer Center, Kansas City, KS 66160, USASchool of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003, USAGrand Forks Human Nutrition Research Center, Agricultural Research Service, United States Department of Agriculture, Grand Forks, ND 58203, USAConsumption of a high-fat diet (HFD) links obesity to colon cancer in humans. Our data show that a HFD (45% energy fat versus 16% energy fat in an AIN-93 diet (AIN)) promotes azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) formation in a mouse cancer model. However, the underlying metabolic basis remains to be determined. In the present study, we hypothesize that AOM treatment results in different plasma metabolomic responses in diet-induced obese mice. An untargeted metabolomic analysis was performed on the plasma samples by gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). We found that 53 of 144 identified metabolites were different between the 4 groups of mice (AIN, AIN + AOM, HFD, HFD + AOM), and sparse partial least-squares discriminant analysis showed a separation between the HFD and HFD + AOM groups but not the AIN and AIN + AOM groups. Moreover, the concentrations of dihydrocholesterol and cholesterol were inversely associated with AOM-induced colonic ACF formation. Functional pathway analyses indicated that diets and AOM-induced colonic ACF modulated five metabolic pathways. Collectively, in addition to differential plasma metabolomic responses, AOM treatment decreases dihydrocholesterol and cholesterol levels and alters the composition of plasma metabolome to a greater extent in mice fed a HFD compared to the AIN.https://www.mdpi.com/2218-1989/11/7/448aberrant crypt fociazoxymethanecolon cancerhigh-fat dietinflammationmetabolome |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Huawei Zeng Shahid Umar Zhenhua Liu Michael R. Bukowski |
spellingShingle |
Huawei Zeng Shahid Umar Zhenhua Liu Michael R. Bukowski Azoxymethane Alters the Plasma Metabolome to a Greater Extent in Mice Fed a High-Fat Diet Compared to an AIN-93 Diet Metabolites aberrant crypt foci azoxymethane colon cancer high-fat diet inflammation metabolome |
author_facet |
Huawei Zeng Shahid Umar Zhenhua Liu Michael R. Bukowski |
author_sort |
Huawei Zeng |
title |
Azoxymethane Alters the Plasma Metabolome to a Greater Extent in Mice Fed a High-Fat Diet Compared to an AIN-93 Diet |
title_short |
Azoxymethane Alters the Plasma Metabolome to a Greater Extent in Mice Fed a High-Fat Diet Compared to an AIN-93 Diet |
title_full |
Azoxymethane Alters the Plasma Metabolome to a Greater Extent in Mice Fed a High-Fat Diet Compared to an AIN-93 Diet |
title_fullStr |
Azoxymethane Alters the Plasma Metabolome to a Greater Extent in Mice Fed a High-Fat Diet Compared to an AIN-93 Diet |
title_full_unstemmed |
Azoxymethane Alters the Plasma Metabolome to a Greater Extent in Mice Fed a High-Fat Diet Compared to an AIN-93 Diet |
title_sort |
azoxymethane alters the plasma metabolome to a greater extent in mice fed a high-fat diet compared to an ain-93 diet |
publisher |
MDPI AG |
series |
Metabolites |
issn |
2218-1989 |
publishDate |
2021-07-01 |
description |
Consumption of a high-fat diet (HFD) links obesity to colon cancer in humans. Our data show that a HFD (45% energy fat versus 16% energy fat in an AIN-93 diet (AIN)) promotes azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) formation in a mouse cancer model. However, the underlying metabolic basis remains to be determined. In the present study, we hypothesize that AOM treatment results in different plasma metabolomic responses in diet-induced obese mice. An untargeted metabolomic analysis was performed on the plasma samples by gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). We found that 53 of 144 identified metabolites were different between the 4 groups of mice (AIN, AIN + AOM, HFD, HFD + AOM), and sparse partial least-squares discriminant analysis showed a separation between the HFD and HFD + AOM groups but not the AIN and AIN + AOM groups. Moreover, the concentrations of dihydrocholesterol and cholesterol were inversely associated with AOM-induced colonic ACF formation. Functional pathway analyses indicated that diets and AOM-induced colonic ACF modulated five metabolic pathways. Collectively, in addition to differential plasma metabolomic responses, AOM treatment decreases dihydrocholesterol and cholesterol levels and alters the composition of plasma metabolome to a greater extent in mice fed a HFD compared to the AIN. |
topic |
aberrant crypt foci azoxymethane colon cancer high-fat diet inflammation metabolome |
url |
https://www.mdpi.com/2218-1989/11/7/448 |
work_keys_str_mv |
AT huaweizeng azoxymethanealterstheplasmametabolometoagreaterextentinmicefedahighfatdietcomparedtoanain93diet AT shahidumar azoxymethanealterstheplasmametabolometoagreaterextentinmicefedahighfatdietcomparedtoanain93diet AT zhenhualiu azoxymethanealterstheplasmametabolometoagreaterextentinmicefedahighfatdietcomparedtoanain93diet AT michaelrbukowski azoxymethanealterstheplasmametabolometoagreaterextentinmicefedahighfatdietcomparedtoanain93diet |
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