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 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.

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Azoxymethane Alters the Plasma Metabolome to a Greater Extent in Mice Fed a High Fat Diet Compared to AIN-93 Diet

Current Developments in Nutrition ◽

10.1093/cdn/nzab036_031 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 289-289

Author(s):

Huawei Zeng ◽

Shahid Umar ◽

Zhenhua Liu ◽

Michael Bukowski

Keyword(s):

Colon Cancer ◽

High Fat Diet ◽

Agricultural Research ◽

Tca Cycle ◽

Aberrant Crypt Foci ◽

Alpha Tocopherol ◽

Service Research ◽

Cancer Model ◽

High Fat ◽

Plasma Metabolome

Abstract Objectives Consumption of a high fat diet (HFD) links obesity to colon cancer in humans. Consistent with this observation, our data show that a HFD (45% energy fat versus 16% energy fat in 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. We hypothesize that AOM treatment results in different plasma metabolomic responses in AOM mouse colon cancer model fed with a HFD compared to the AIN. Methods Four-week-old male C57BL/6 mice were fed the AIN or HFD in the context of with or without AOM treatment for 16 weeks. At the end of this study, plasma samples were extracted and derivatized by silylation and methyloximation then analyzed by time-of-flight mass spectrometry using an untargeted metabolomic technique. Results Untargeted metabolomic profiling showed that 53 of 144 identified metabolites were different between the 4 groups of mice (AIN only, AIN + AOM; HFD only, HFD + AOM). Sparse partial least squares discriminant analysis (two-dimensional plots) showed a separation between the HFD and HFD + AOM groups but not AIN and AIN + AOM groups. Major metabolites responsible for this separation were beta-sitosterol, dihydrocholesterol, alpha-tocopherol, methylphosphate, citric acid, cholesterol, isocitric acid, myristic acid, arachidonic acid, and nicotinamide. Importantly, the levels of dihydrocholesterol and cholesterol were inversely associated with AOM-induced colonic ACF formation. Functional pathway and enrichment analyses indicated that diets and AOM-induced colonic ACF modulated 5 metabolic pathways: (a) citrate cycle (TCA cycle), (b) arginine biosynthesis, (c) aminoacyl-tRNA biosynthesis, (d) alanine, aspartate and glutamate metabolism, (e) glyoxylate and dicarboxylate metabolism. Conclusions Collectively, we demonstrate that AOM 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. Funding Sources This work was supported by U.S. Department of Agriculture, Agricultural Research Service, research project 3062-51000-056-00D.

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Pengaruh Pemberian Terapi Oksigen Hiperbarik Terhadap Kadar Kolesterol Total Pada Tikus Putih (Rattus novergicus) Jantan Galur Wistar Yang Di Induksi Diet Tinggi Lemak

Hang Tuah Medical journal ◽

10.30649/htmj.v16i1.56 ◽

2018 ◽

Vol 16 (1) ◽

pp. 1 ◽

Cited By ~ 1

Author(s):

AZRUL HILDAN SAFRIZAL

Keyword(s):

Cardiovascular Disease ◽

Total Cholesterol ◽

Cholesterol Level ◽

Hyperbaric Oxygen ◽

Hyperbaric Oxygen Therapy ◽

High Fat Diet ◽

Oxygen Therapy ◽

Total Cholesterol Level ◽

High Fat ◽

Cholesterol Levels

<p>The pattern and lifestyle of today's society with the presence of an interner facility makes people spend more time sitting out than on exercise and increased consumption of high-fat foods may increase the risk of cardiovascular disease. An effective therapy is needed in preventing the occurrence of cardiovascular disease. Hyperbaric oxygen now starts to develop for the treatment of several diseases, which in turn can increase the gene forming antioxidant enzymes and ROS. To determine effect of hyperbaric oxygen therapy on total cholesterol levels of wistar white rats (Rattusnovergicus) induced bye high fat. The study was carried out in an expeative post test only group control of three groups. One group is given standard feed. All groups induced high-fat diet and standard feed. Of the two groups induced, one group was given hyperbaric oxygen therapy with a dose of 3 x 30 minutes for six days on day 7 at a blood test to determine total cholesterol levels<strong>. </strong>One way Anova parametric statistic test showed that p = 0.007 < α proved hypothesis that hyperbaric oxygen therapy giving effect to total cholesterol level of white mice of jantangalurist rings induced by high fat diet. Total cholesterol was significantly different between K (-) and K (+) and between K (-) and P. It was found that hyperbaric oxygen therapy had an effect on total cholesterol level dose of 3x30 minutes for six days.</p>

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Anti-Obesity and Hypocholesterolemic Actions of Protamine-Derived Peptide RPR (Arg-Pro-Arg) and Protamine in High-Fat Diet-Induced C57BL/6J Mice

Nutrients ◽

10.3390/nu13082501 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2501

Author(s):

Maihemuti Mijiti ◽

Ryosuke Mori ◽

Bingyu Huang ◽

Kenichiro Tsukamoto ◽

Keisuke Kiriyama ◽

...

Keyword(s):

Adipose Tissue ◽

High Fat Diet ◽

Fecal Excretion ◽

Control Group ◽

High Fat ◽

Tissue Weight ◽

Cholesterol Levels ◽

Adipose Tissue Weight ◽

Fas Mrna ◽

Hypocholesterolemic Peptide

Dietary protamine can ameliorate hyperlipidemia; however, the protamine-derived active peptide and its hypolipidemic mechanism of action are unclear. Here, we report the discovery of a novel anti-obesity and hypocholesterolemic peptide, RPR (Arg-Pro-Arg), derived from protamine in mice fed a high-fat diet for 50 days. Serum cholesterol levels were significantly lower in the protamine and RPR groups than in the control group. White adipose tissue weight was significantly decreased in the protamine and RPR groups. The fecal excretion of cholesterol and bile acid was significantly higher in the protamine and RPR groups than in the control group. We also observed a significant decrease in the expression of hepatic SCD1, SREBP1, and adipocyte FAS mRNA, and significantly increased expression of hepatic PPARα and adipocyte PPARγ1 mRNA in the protamine group. These findings demonstrate that the anti-obesity effects of protamine are linked to the upregulation of adipocyte PPARγ1 and hepatic PPARα and the downregulation of hepatic SCD1 via SREBP1 and adipocyte FAS. RPR derived from protamine has a crucial role in the anti-obesity action of protamine by evaluating the effective dose of adipose tissue weight loss.

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Effect of Soybean and Soybean Koji on Obesity and Dyslipidemia in Rats Fed a High-Fat Diet: A Comparative Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18116032 ◽

2021 ◽

Vol 18 (11) ◽

pp. 6032

Author(s):

Sihoon Park ◽

Jae-Joon Lee ◽

Hye-Won Shin ◽

Sunyoon Jung ◽

Jung-Heun Ha

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

High Fat Diet ◽

Unsaturated Fatty Acids ◽

Density Lipoprotein ◽

Serum Triglyceride ◽

Lipoprotein Cholesterol ◽

Health Concern ◽

High Fat ◽

Cholesterol Levels

Soybean koji refers to steamed soybeans inoculated with microbial species. Soybean fermentation improves the health benefits of soybeans. Obesity is a serious health concern owing to its increasing incidence rate and high association with other metabolic diseases. Therefore, we investigated the effects of soybean and soybean koji on high-fat diet-induced obesity in rats. Five-week-old male Sprague-Dawley rats were randomly divided into four groups (n = 8/group) as follows: (1) regular diet (RD), (2) high-fat diet (HFD), (3) HFD + steamed soybean (HFD+SS), and (4) HFD + soybean koji (HFD+SK). SK contained more free amino acids and unsaturated fatty acids than SS. In a rat model of obesity, SK consumption significantly alleviated the increase in weight of white adipose tissue and mRNA expression of lipogenic genes, whereas SS consumption did not. Both SS and SK reduced serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels, and increased high-density lipoprotein cholesterol levels. SS and SK also inhibited lipid accumulation in the liver and white adipose tissue and reduced adipocyte size. Although both SS and SK could alleviate HFD-induced dyslipidemia, SK has better anti-obesity effects than SS by regulating lipogenesis. Overall, SK is an excellent functional food that may prevent obesity.

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Dietary Aloe Vera Gel Powder and Extract Inhibit Azoxymethane-induced Colorectal Aberrant Crypt Foci in Mice Fed a High-fat Diet

Asian Pacific Journal of Cancer Prevention ◽

10.7314/apjcp.2015.16.2.683 ◽

2015 ◽

Vol 16 (2) ◽

pp. 683-687 ◽

Cited By ~ 2

Author(s):

Takeshi Chihara ◽

Kan Shimpo ◽

Takaaki Kaneko ◽

Hidehiko Beppu ◽

Takashi Higashiguchi ◽

...

Keyword(s):

High Fat Diet ◽

Aloe Vera ◽

Aberrant Crypt Foci ◽

High Fat ◽

Aloe Vera Gel

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High-Fat Diet Alters Gene Expression in the Liver and Colon: Links to Increased Development of Aberrant Crypt Foci

Digestive Diseases and Sciences ◽

10.1007/s10620-012-2092-9 ◽

2012 ◽

Vol 57 (7) ◽

pp. 1866-1874 ◽

Cited By ~ 29

Author(s):

Sara Padidar ◽

Andrew J. Farquharson ◽

Lynda M. Williams ◽

Rebecca Kearney ◽

John R. Arthur ◽

...

Keyword(s):

Gene Expression ◽

High Fat Diet ◽

Aberrant Crypt Foci ◽

High Fat

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Insulin resistance and promotion of aberrant crypt foci in the colons of rats on a high‐fat diet

Nutrition and Cancer ◽

10.1080/01635589709514604 ◽

1997 ◽

Vol 29 (1) ◽

pp. 69-76 ◽

Cited By ~ 55

Author(s):

Niloofar Koohestani ◽

Thien T. Tran ◽

Winnie Lee ◽

Thomas M. S. Wolever ◽

W. Robert Bruce

Keyword(s):

Insulin Resistance ◽

High Fat Diet ◽

Aberrant Crypt Foci ◽

High Fat

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The Correlation of Weight and Blood Cholesterol Levels of White Rat (Rattus Norvegicus) with High-Fat Diet

Jurnal Ners dan Kebidanan (Journal of Ners and Midwifery) ◽

10.26699/jnk.v3i3.art.p202-206 ◽

2016 ◽

Vol 3 (3) ◽

pp. 202-206

Author(s):

Thatit Nurmawati

Keyword(s):

Body Weight ◽

Rattus Norvegicus ◽

High Fat Diet ◽

Egg Yolk ◽

The Body ◽

Blood Cholesterol ◽

High Fat ◽

Data Measurement ◽

Cholesterol Levels

Cholesterol is an essential substance for the body. The role of cholesterol as material hormones,cell membranare needed by the body. This conditionchanges into a distrubtion if the cholesterollevels in the blood increase. Weight becomes one of this trigger. The consumption of high-fat foodsincrease weight which resulting in the increase of cholesterol cases. The purpose of this study was todetermine the level of correlations between weight and cholesterol levels after being given a high-fatdiet.The study used rats (Rattus norvegicus) sex male, 16 rats with age between 1-2 months. Rats weightrange between 100-150 gr and in healthy conditions. The giving of high-fat diet were in the form ofchicken feed, duck eggs, goat oil, lard and flour for 8 weeks. The data measurement done by scales andmeasuringcholesterol levels through the end of the tail by means of easy touch. The data analysis weredone to understand level of correlation between variables. The presentation of the data used tables. Theresults showed body weight of rats did not change after administration of a high-fat diet. The cholesterolslevels of the subjects were high. Theadministration of high-fat diet from egg yolk dan goat oilcouldincrease the level of cholesterol. There was a correlation between weight and cholesterol levels afterbeing given a high-fat diet (p <0.5). It was needed to repeatthe measurements to determine changes incholesterol levels and other factors that affect thigh blood to cholesterol levels.

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Serum Metabolomics Analysis for Biomarkers of Lactobacillus plantarum FRT4 in High-Fat Diet-Induced Obese Mice

Foods ◽

10.3390/foods11020184 ◽

2022 ◽

Vol 11 (2) ◽

pp. 184

Author(s):

Hongying Cai ◽

Zhiguo Wen ◽

Xin Xu ◽

Jiaxin Wang ◽

Xuan Li ◽

...

Keyword(s):

Lactobacillus Plantarum ◽

High Fat Diet ◽

Ultra Performance Liquid Chromatography ◽

Leukotriene B4 ◽

Arachidonic Acid Metabolism ◽

High Fat ◽

Flight Mass Spectrometry ◽

Obesity In Mice ◽

Gut Microbiota Dysbiosis ◽

Serum Metabolomics

Lactobacillus plantarum is considered a potential probiotic supplementation for treating obesity. However, the underlying molecular mechanism is poorly understood. Our previous study displayed that L. plantarum FRT4 alleviated obesity in mice fed a high-fat diet (HFD) through ameliorating the HFD-induced gut microbiota dysbiosis. To explore the roles of FRT4 in obesity prevention, in this study, we investigated changes in serum metabolomic phenotype by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) and analyzed the pathway of HFD-fed Kunming female mice orally administered with FRT4 for eight weeks. Using orthogonal partial least squares discriminant analysis (OPLS-DA), metabolite patterns with significant changes were observed. 55 metabolites including phosphatidylcholine, lysophophatidylcholine, sphingomyelin, serotonin, indole-3-methyl aceta, indole-3-carbinol, indole-5,6-quino, 11,12-DHET, prostaglandin B2, leukotriene B4, and 3-hydroxybenzoic acid were identified as potential biomarkers associated with obesity, which were mainly involving in glycerophospholipid metabolism, tryptophan metabolism, and arachidonic acid metabolism. Perturbations of 14 biomarkers could be regulated by FRT4 intervention. These metabolites may serve as valuable biomarkers to understand the mechanisms by which intake of diets containing FRT4 contributes to the treatment or prevention of obesity. Thus, FRT4 can be a promising dietary supplement for the prevention of HFD-induced obesity.

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