scholarly journals The Influence of High-Fat Diet in Early Life on Intestinal Tumorigenesis in APC1638N Mice

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 272-272
Author(s):  
Ting-Chun Lin ◽  
Ying Tang ◽  
Soonkyu Chung ◽  
Young-Cheul Kim ◽  
Zhenhua Liu

Abstract Objectives Colorectal cancer (CRC) is one of the most prevalent cancer worldwide. Evidence from epidemiological studies shows that the incidence rate of CRC among elders with age ≥ 50 years is gradually decreased, whereas the rate continuously rise in adults with age < 50 years. Along with the rise of CRC in young adults, a significantly increasing trend in obesity is also observed in youth. The present study aims to investigate how the early-life nutrition influences the intestinal tumorigenesis later in mouse with an age equivalent to an age < 50 years in human. Methods APC1638N mice (4 weeks of age) were fed a low-fat diet (N = 22; LF: 10% kcal from fat) or a high-fat diet (N = 23; HF: 60% kcal from fat) for 8 weeks, which is equivalent to child/adolescent age in humans. After that, all animals were switched to standard chow diet (LabDiet #5P76) and fed for additional 12 weeks before sacrifice. Tumors were examined and the expression tumorigenic Wnt-signaling downstream genes (Cyclin D1, c-Myc and Axin 2) in the intestine were assessed. Results Our results showed that compared to LF group, the body weight of both male and female mice significantly increased after 8-week HF feeding (P < 0.05). After switching to the standard chow diet for further 12 weeks feeding, the increase of body weight in HF group remained, although the degree of magnitude reduced, and a statistical significance only shown in female mice (P < 0.05). There were a higher tumor incidence (P = 0.051) and tumor multiplicity (P < 0.05) in males than female.  No interactions between gender and diet were observed. The HF group had a higher tumor incidence (P = 0.088) and tumor size (P < 0.05) when compared to the LF group. The expression of Wnt-signaling downstream gene, c-Myc, was significantly increased in the HF group at 24-week of age (P < 0.01). Conclusions A short term of high-fat diet in early life tends to promote intestinal tumorigenesis in adults as indicated by a mild increase in tumor incidence and a significant increase in tumor size. Funding Sources This project was supported by the US Department of Agriculture Hatch funding (#1013548).

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 54-54
Author(s):  
Ying Tang ◽  
Ting-Chun Lin ◽  
Soonkyu Chung ◽  
Young-Cheul Kim ◽  
Zhenhua Liu

Abstract Objectives Emerging evidence indicates a potentially important role for early-life events and exposures in cancer development later in life. Moreover, accumulating evidence suggests that the incidence of cancers has reached a plateau in elders, whereas it continuously rises in young to middle adult. The present study aimed to investigate the potential impacts of high-fat diet in early-life, mimicking childhood/adolescent in humans, on mammary health in later-life of mice, equivalent to the young to middle age in human. Methods Female C57BL/8 mice (4 weeks of age) were fed a low-fat diet (LF: 10% kcal from fat) or a high-fat diet (HF: 60% kcal from fat) for 8 weeks, which is equivalent to child/adolescent age in humans. Mice in early-life groups were sacrificed after 8 weeks feeding, whereas mice in later-life groups were switched to standard chow diet (Lab Diet#5P76) and fed for additional 12 weeks before sacrifice. A panel of metabolic parameters, inflammatory cytokines, as well as gene expression related to tumorigenic Wnt-signaling were assessed by qPCR and immunoblotting analysis. Results Compared with LF group, the body weight in HF group was significantly elevated after 8-wk HF diet feeding (P < 0.05). After switching to the standard chow diet for 12 weeks, the significance remained until 24 weeks of age although with a reduced degree of magnitude (P < 0.05). For the metabolic factors, HFD reduced the expression levels of both Pparγ (P = 0.08) and adiponectin (P < 0.05) at 12 weeks and the reductions remains at 24 weeks (P < 0.01). Meanwhile, expressions of aromatase, estrogen receptor α and Tnf-α, Il-6, Il-10 as well as Cox2 among examined inflammatory mediators (Tnf-α, Il-6, Il-10, Il-2, Il-1β, Ifn-γ, Cox2) were significantly higher in HF than in LF group at 24 weeks (P < 0.05). For Wnt-signaling target genes (Cyclin D1, C-Myc, and Axin 2), a significant increase for C-Myc was observed in HF group at 12 weeks (P < 0.01). Conclusions Our results suggested that HF diet in early-life enhances adiposity and alters mammary metabolic and inflammatory status, creating a microenvironment in favor of breast tumorigenesis in later-life. Funding Sources This project was supported by USDA/Hatch (#1013548).


Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Mohammed A Khan ◽  
Preethi Samuel ◽  
Sourashish Nag ◽  
Tahir Hussain

Obesity in itself is a disease condition and a major risk factor in the development of hypertension, dyslipidemia, and hyperglycemia. Therefore, successful strategies for improving obesity and related metabolic risk factors are needed. Role of renin-angiotensin system (RAS) has been implicated in obesity and metabolic dysfunction. Recently, we have shown that AT2R knock-out in female mice caused a greater body weight gain and hyperinsulimia in response to high fat diet (HFD). In the present study, we hypothesize that AT2R activation rescues diet-induced obesity in females. To test this hypothesis, we injected AT2R non-peptide agonist C21 (0.3mg/kg/day i.p) in C57BL6 female mice on HFD for 12 weeks. C21-treatment did not affect the HFD calorie intake (HFD: 937±18 Kcal; C21HFD: 886±37 Kcal) but caused lesser body weight gain compared to control (HFD: 4.4± 0.4g; C21HFD: 3.06± 0.4g). Similar to the body weight gain pattern, gonadal fat weight and adipocyte size were decreased significantly in C21-treated mice on HFD compared to control HFD group (HFD: 4.4± 0.4 g; C21 HFD: 3.06± 0.4g) and (HFD: 6404±161.6μm2 ; C21HFD: 3874±103.2μm2 ) respectively. Moreover, the C21-treated females on HFD had lower levels of plasma insulin, improved glucose tolerance, and decreased plasma free fatty acids and hepatic triglycerides. Western blot revealed that phospho-Ser79-acetyl CoA carboxylase (p-Ser79-ACC-1) was reduced, an index of increased lipogenic activity and decreased β-oxidation process, in both adipose (Adi) and hepatic (Hep) tissues of HFD fed groups (Adi: 86% and Hep: 73% of 100% controls); C21-treatment revered the decrease in p-ser79-ACC-1 in Adi (104% of control) and caused an increase in Hep (122% of control) respectively. The HFD feeding lowered the estradiol level (ND: 38.8±2.6 vs HFD:11.3±1.2ng), which was modestly reversed by C21 treatment (C21HFD:17.4± 1.5ng) in HFD mice. Our results strongly suggest that stimulation of AT2R in female mice positively contribute, predominantly independent of estrogen, to rescue body weight gain and adipocyte size increase in response to HFD. We propose reduced lipogenesis and enhanced lipid β-oxidation as potential mechanisms linked to AT2R action in reducing obesity and its related metabolic disorders in females.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Souravh Bais ◽  
Guru Sewak Singh ◽  
Ramica Sharma

In the present study, the methanolic extract of Moringa oleifera leaves (MEMOL) was evaluated for antiobesity activity in rats. The antiobesity potential of MEMOL was studied against high fat diet-induced obesity (HFD) in rats. In this study, chronic administration of HFD in rats produced hypercholesterolemia (116.2 ± 0.27 mg/dL), which led to an increase in the body weight (225 gr), total cholesterol, triglycerides (263.0 ± 4.69 mg/dL), and attenuation in the levels of HDL (34.51 ± 2.20 mg/dL) as well as changes in body temperature of animals. Treatment of obese rats with MEMOL for 49 days resulted in a significant (P<0.001) change in body weight, total cholesterol, triglycerides, and LDL level along with a significant (P<0.001) increase in body temperature as compared to the HFD-induced obesity. MEMOL treated rats also showed a significant decrease in the level of liver biomarkers, organ weight, and blood glucose level. Further, rats treated with MEMOL (200 mg and 400 mg/kg) show reduced atherogenic index (1.7 ± 0.6 and 0.87 ± 0.76). The results indicate that the rats treated with Moringa oleifera (MO) have significantly attenuated the body weight without any change in the feed intake and also elicited significant thermogenic effect and to act as hypolipidemic and thermogenic property in obesity related disorders.


Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 99 ◽  
Author(s):  
Wang Ling ◽  
Shungeng Li ◽  
Xingcai Zhang ◽  
Yongquan Xu ◽  
Ying Gao ◽  
...  

: Probiotic dark tea (PDT) is a novel kind of dark tea produced by fresh albino tea leaves and fermented with specific probiotics. Our study demonstrates that PDT can ameliorate high-fat diet-induced overweight and lipid metabolic disorders and shows no acute or subacute toxicity in Sprague-Dawley (SD) rats. Daily intragastric administration of 5% PDT infusion for 14 days caused no obvious effect on general physiological features and behaviors of rats. Oral administration of 1%, 2%, and 3% of PDT infusion for six weeks had no influence on the biochemistry and histopathology of rats’ organs and blood, as well as the body weight and ratios of organ/body weight. To investigate its anti-obesity activity, SD rats were randomly divided into four groups, treated with normal diet + water (Group I), high-fat diet + water (Group II), high-fat diet + 3% traditional dark tea infusion (Group III), high-fat diet + 3% PDT infusion (Group IV). After six weeks, the body weight, serum total triacylglycerol (TG) and serum total cholesterol (TC) levels of rats in Group II were significantly increased and the high-density lipoprotein cholesterol (HDL) levels were significantly decreased compared with those in the other three groups. Both traditional dark tea and PDT treatment effectively counteracted the adverse effect of a high-fat diet in SD rats. These results suggest that PDT could be applied for the prevention of obesity, which ameliorates overweight and lipid metabolic disorders and which shows no acute or subacute toxicity.


2014 ◽  
Vol 9 (10) ◽  
pp. 1934578X1400901 ◽  
Author(s):  
Qing Liu ◽  
Sang Hyun Kim ◽  
Seon Beom Kim ◽  
Yang Hee Jo ◽  
Eun Sil Kim ◽  
...  

The effect of the extract of Ligustrum lucidum fruits (LFE) and its major secoiridoid (LFS), (8- E)-nüzhenide, on obesity was investigated using high fat-diet (HFD)-induced C58BL/6J obese mice. LFE and LFS were administered at the doses of 300 mg/kg and 30 mg/kg, respectively, for 6 weeks. The anti-obesity activity was evaluated by measuring body weight, epididymal fat and metabolic plasma parameters. On Day 42, the body weight of the LFS-treated group was significantly lower compared with the HFD-treated group. Body weight gain was also reduced by 23.2% and 32.0% in the LFE- and LFS-treated groups, respectively, compared with the HFD group. In addition, the weight of the epididymal fat in the mice was significantly decreased in the HFD+LFS group. The food efficiency ratios (FERs) of the HFD+LFE and HFD+LFS groups were also lower compared with the HFD group with the same food intake. Metabolic parameters that had increased in the HFD group were decreased in the HFD+LFE and HFD+LFS groups. In particular, the increased triglyceride values were significantly reduced in the HFD+LFS group. These results show that treatment with LFE and LFS decreased HFD-induced obesity, mainly by improving metabolic parameters, such as fats and triglycerides. Therefore, LFE and LFS have potential benefits in regulation of obesity.


2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Jaqueline R. Leachman ◽  
Eva Gatineau ◽  
Madhur Agarwal ◽  
Carolina Dalmasso ◽  
Xiu Xu ◽  
...  

2018 ◽  
Vol 50 (8) ◽  
pp. 605-614
Author(s):  
Hong He ◽  
Katie Holl ◽  
Sarah DeBehnke ◽  
Chay Teng Yeo ◽  
Polly Hansen ◽  
...  

Type 2 diabetes is a complex disorder affected by multiple genes and the environment. Our laboratory has shown that in response to a glucose challenge, two-pore channel 2 ( Tpcn2) knockout mice exhibit a decreased insulin response but normal glucose clearance, suggesting they have improved insulin sensitivity compared with wild-type mice. We tested the hypothesis that improved insulin sensitivity in Tpcn2 knockout mice would protect against the negative effects of a high fat diet. Male and female Tpcn2 knockout (KO), heterozygous (Het), and wild-type (WT) mice were fed a low-fat (LF) or high-fat (HF) diet for 24 wk. HF diet significantly increases body weight in WT mice relative to those on the LF diet; this HF diet-induced increase in body weight is blunted in the Het and KO mice. Despite the protection against diet-induced weight gain, however, Tpcn2 KO mice are not protected against HF-diet-induced changes in glucose or insulin area under the curve during glucose tolerance tests in female mice, while HF diet has no significant effect on glucose tolerance in the male mice, regardless of genotype. Glucose disappearance during an insulin tolerance test is augmented in male KO mice, consistent with our previous findings suggesting enhanced insulin sensitivity in these mice. Male KO mice exhibit increased fasting plasma total cholesterol and triglyceride concentrations relative to WT mice on the LF diet, but this difference disappears in HF diet-fed mice where there is increased cholesterol and triglycerides across all genotypes. These data demonstrate that knockout of Tpcn2 may increase insulin action in male, but not female, mice. In addition, both male and female KO mice are protected against diet-induced weight gain, but this protection is likely independent from glucose tolerance, insulin sensitivity, and plasma lipid levels.


PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e55603 ◽  
Author(s):  
Mirjam Luijten ◽  
Amar V. Singh ◽  
Caleb A. Bastian ◽  
Anja Westerman ◽  
M. Michele Pisano ◽  
...  

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1216-1216
Author(s):  
Xinge Hu

Abstract Objectives The dietary fat content plays an important role in the regulation of chronic metabolic diseases such as obesity and type 2 diabetes. Here, we tested the impacts of triacylglycerol structure on the body weight gain and food intake of mice in a high-fat diet (HFD) setting. Methods Male C57/BL6J mice at 6 weeks old were fed one of the following three diets for 6 weeks, Teklad Rodent Diet chow diet (number 8640), the chow diet containing 36% (w/w) 1,2-Dipalmitoyl-3-oleoylglycerol (PPO), or the chow diet containing 36% (w/w) 1,3-Dipalmitoyl-2-oleoylglycerol (POP). Each group contained 9 mice, and their food intake and BW were measured daily. The mice were euthanized after 6 weeks (12 weeks old) for tissue sample collection. Results Both high HFD groups had significantly higher BW gain and caloric intakes than the chow diet group. Mice fed the POP diet had a lower percentage of BW gain and consumed less accumulated calories than those fed the PPO diet, as well as a significantly lower liver to BW ratio. Since week 4, the body BW rate of the POP group started to be lower than that of the PPO diet group. Conclusions TAG structures in an HFD setting affect the BW gain rate and obesity in mice. The different structures of fat added to affect the food intake and BW gain differently in an HFD setting. In the future, we would like to compare the changes of the hepatic lipogenesis enzyme in these mice. This will help us to understand how the triacylglycerol structures in the diet affect lipid metabolism in mice. Funding Sources Internal.


2016 ◽  
Vol 3 (3) ◽  
pp. 202-206
Author(s):  
Thatit Nurmawati

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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