scholarly journals Diet-Dependent Changes of the DNA Methylome Using a Göttingen Minipig Model for Obesity

2021 ◽  
Vol 12 ◽  
Author(s):  
Y. Feng ◽  
S. Cirera ◽  
E. Taşöz ◽  
Y. Liu ◽  
L. H. Olsen ◽  
...  

Objective: Environmental factors can influence obesity by epigenetic mechanisms. The aim of this study was to investigate obesity-related epigenetic changes and the potential for reversal of these changes in the liver of Göttingen minipigs subjected to diet interventions.Methods: High-throughput liquid hybridization capture-based bisulfite sequencing (LHC-BS) was used to quantify the methylation status of gene promotor regions in liver tissue in three groups of male castrated Göttingen minipigs: a standard chow group (SD, N = 7); a group fed high fat/fructose/cholesterol diet (FFC, N = 10) and a group fed high fat/fructose/cholesterol diet during 7 months and reversed to standard diet for 6 months (FFC/SD, N = 12). Expression profiling by qPCR of selected metabolically relevant genes was performed in liver tissue from all pigs.Results: The pigs in the FFC diet group became morbidly obese. The FFC/SD diet did not result in a complete reversal of the body weight to the same weight as in the SD group, but it resulted in reversal of all lipid related metabolic parameters. Here we identified widespread differences in the patterning of cytosine methylation of promoters between the different feeding groups. By combining detection of differentially methylated genes with a rank-based hypergeometric overlap algorithm, we identified 160 genes showing differential methylation in corresponding promoter regions in the FFC diet group when comparing with both the SD and FFC/SD groups. As expected, this differential methylation under FFC diet intervention induced de-regulation of several metabolically-related genes involved in lipid/cholesterol metabolism, inflammatory response and fibrosis generation. Moreover, five genes, of which one is a fibrosis-related gene (MMP9), were still perturbed after diet reversion.Conclusion: Our findings highlight the potential of exploring diet-epigenome interactions for treatment of obesity.

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Ana Paula Lima-Leopoldo ◽  
Artur Ferron ◽  
Bruno Jacobsen ◽  
Dijon Campos ◽  
Renata Luvizotto ◽  
...  

Several structural and functional changes of the heart have often been associated with human and experimental models of obesity. Some factors have been suggested as responsible for possible cardiac abnormalities in models of obesity, among them β-adrenergic system, an important mechanism of regulation of myocardial contraction and relaxation. The objetive of present study was to evaluate the . Thirty-day-old male Wistar rats were assigned to one of two groups: control (C) and obese (Ob). The C group was fed a standard diet and Ob group was fed cycles of four unsaturated high-fat diets for 15 weeks. The body fat was measured from the sum of the individual fat pad weights and the obesity was defined by adiposity index. Isolated papillary muscle preparation was performed under basal conditions and after inotropic and lusitropic maneuvers. β-adrenergic system was evaluated by using cumulative concentrations of isoproterenol and Western Blot. After 15 weeks, the Ob rats developed higher adiposity index than C rats. Obesity promoted comorbities such as glucose intolerance, insulin resistance, hyperleptinemia, and dyslipidemia; however, were not associated with changes in systolic blood pressure. The cardiac structure results post-death showed that obesity caused cardiac hypertrophy. Furthermore, Ob muscles developed similar baseline data, but myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca2+ was compromised. There were no changes in cardiac function between groups after β-adrenergic stimulation. The obesity was not accompanied by changes in protein expression of Gsα, β1 and β2 adrenergic receptors. In conclusion, the myorcardial dysfunction caused by unsaturated high-fat diet-induced obesity, after 15 weeks, is not related to β-adrenergic system impairment.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Guilherme L. da Rocha ◽  
Alex H. Crisp ◽  
Maria R. M. de Oliveira ◽  
Carlos A. da Silva ◽  
Jadson O. Silva ◽  
...  

This study aimed to investigate the effects of interval and continuous training on the body mass gain and adiposity levels of rats fed a high-fat diet. Forty-eight male Sprague-Dawley rats were randomly divided into two groups, standard diet and high-fat diet, and received their respective diets for a period of four weeks without exercise stimuli. After this period, the animals were randomly divided into six groups (n=8): control standard diet (CS), control high-fat diet (CH), continuous training standard diet (CTS), continuous training high-fat diet (CTH), interval training standard diet (ITS), and interval training high-fat diet (ITH). The interval and continuous training consisted of a swimming exercise performed over eight weeks. CH rats had greater body mass gain, sum of adipose tissues mass, and lower serum high density lipoprotein values than CS. The trained groups showed lower values of feed intake, caloric intake, body mass gain, and adiposity levels compared with the CH group. No significant differences were observed between the trained groups (CTS versus ITS and CTH versus ITH) on body mass gains and adiposity levels. In conclusion, both training methodologies were shown to be effective in controlling body mass gain and adiposity levels in high-fat diet fed rats.


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.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Valeria Cagnon ◽  
Ellen Lima ◽  
Celina Lamas ◽  
Andressa Baseggio ◽  
Larissa Kido ◽  
...  

Abstract Objectives Brazilian berries, such as Myrciaria jaboticaba (Vell.) Berg, present a high polyphenol concentration in the peel, showing an antioxidative property. The aim herein was to evaluate the antiangiogenic, antioxidant and proliferative effects of the Jaboticaba peel extract (patent BR 1020170054624) in early adenocarcinoma development in association with high-fat diet intake Methods Tramp mice were divided into 5 groups: Control group 8 (C8): 8 week-old mice; Control group 16 (C16): 16 week-old mice, standard diet; High-fat diet group (CH16): 16 week-old mice, high-fat diet; Jaboticaba standard diet group (JC): 16 week-old mice, standard diet and Jaboticaba intake; Jaboticaba high-fat diet group (HF): 16 week-old mice, high-fat diet and Jaboticaba intake. The 5.8 g Jaboticaba/Kg/body weight dose was administered five days per week for 2 months. The prostate was evaluated for proliferative, antiangiogenic and antioxidative markers, using morphology, immunohistochemistry and Western Blotting analyses. Results The prostate showed increased high grade prostatic intraepithelial neoplasia (HGPIN) and well-differentiated adenocarcinoma in the CH16 group. The Jaboticaba peel (JH group) led to decreased HGPIN. In both the JC and JH groups, a frequency increase of healthy prostatic epithelium was verified. A well-differentiated adenocarcinoma decrease was seen in the JC group. PCNA showed an increase in the CH16 group and a decrease in the JH group. VEGF had an increase in the CH16 group and a decrease after Jaboticaba peel extract intake. Catalase, SOD2, GR and 4HNE showed an increase in the CH16 group and all these molecules presented a decrease after Jaboticaba peel intake in the JH group. The TGFα protein level increased in the C16 and CH16 groups and decreased in the JC and JH groups. Conclusions To conclude, the high-fat diet intake intensified the severity of prostatic lesions. The Jaboticaba peel extract was effective in delaying prostatic adenocarcinoma progression, when administered at the early grades of cancer and considering the lesion severity. Jaboticaba peel intake showed antiangiogenic and antioxidant effects in the prostate, especially, after high-fat diet intake in Tramp mice, indicating a possible coadjuvant role of this natural compound in prostatic cancer therapy. Funding Sources Fapesp 18 045797.


2013 ◽  
Vol 110 (8) ◽  
pp. 1421-1428 ◽  
Author(s):  
Jonatan Miranda ◽  
María P. Portillo ◽  
Juan Antonio Madrid ◽  
Noemí Arias ◽  
M. Terasa Macarulla ◽  
...  

In mammals, the main component of the circadian system is the suprachiasmatic nucleus in the hypothalamus. However, circadian clocks are also present in most peripheral tissues, such as adipose tissue. The aim of the present study was to analyse the potential effects of resveratrol on changes induced by high-fat feeding in the expression of clock genes and clock-controlled genes in the white adipose tissue from rats. For this purpose, rats were divided into three groups: a control group, fed a standard diet, and two other groups, either fed a high-fat diet supplemented with resveratrol (RSV) or no resveratrol (HF). The expression of clock genes and clock-controlled genes was analysed by RT-PCR. Protein expression and fatty acid synthase (FAS) activity were also analysed. When comparing the controls, the RSV group showed similar patterns of response to the HF group, except for reverse erythroblastosis virus α (Rev-Erbα), which was down-regulated. The expression of this gene reached the same levels as in control rats. The response pattern of protein expression forRev-Erbαwas similar to that found for gene expression. High-fat feeding up-regulated all adipogenic genes and resveratrol did not modify them. In the HF group, the activity of FAS tended to increase, while resveratrol decreased. In conclusion, resveratrol reverses the change induced by high-fat feeding in the expression ofRev-Erbαin adipose tissue, which means that clock machinery is a target for this polyphenol. This change seems to be related to reduced lipogenesis, which might be involved in the body fat-lowering effect of this molecule.


2008 ◽  
Vol 295 (6) ◽  
pp. E1341-E1348 ◽  
Author(s):  
E. M. E. van Straten ◽  
N. C. A. Huijkman ◽  
J. F. W. Baller ◽  
F. Kuipers ◽  
T. Plösch

Cholesterol is critical for several cellular functions and essential for normal fetal development. Therefore, its metabolism is tightly controlled during all life stages. The liver X receptors-α (LXRα; NR1H3) and -β (LXRβ; NR1H2) are nuclear receptors that are of key relevance in coordinating cholesterol and fatty acid metabolism. The aim of this study was to elucidate whether fetal cholesterol metabolism can be influenced in utero via pharmacological activation of LXR and whether this would have long-term effects on cholesterol homeostasis. Administration of the LXR agonist T0901317 to pregnant mice via their diet (0.015% wt/wt) led to induced fetal hepatic expression levels of the cholesterol transporter genes Abcg5/g8 and Abca1, higher plasma cholesterol levels, and lower hepatic cholesterol levels compared with controls. These profound changes during fetal development did not affect cholesterol metabolism in adulthood nor did they influence coping with a high-fat/high-cholesterol diet. This study shows that the LXR system is functional in fetal mice and susceptible to pharmacological activation. Despite massive changes in fetal cholesterol metabolism, regulatory mechanisms involved in cholesterol metabolism return to a “normal” state in offspring and allow coping with a high-fat/high-cholesterol diet.


2008 ◽  
Vol 295 (1) ◽  
pp. G203-G208 ◽  
Author(s):  
Astrid E. van der Velde ◽  
Carlos L. J. Vrins ◽  
Karin van den Oever ◽  
Ingar Seemann ◽  
Ronald P. J. Oude Elferink ◽  
...  

Biliary secretion is generally considered to be an obligate step in the pathway of excess cholesterol excretion from the body. We have recently shown that an alternative route exists. Direct transintestinal cholesterol efflux (TICE) contributes significantly to cholesterol removal in mice. Our aim was to investigate whether the activity of this novel pathway can be influenced by dietary factors. In addition, we studied the role of cholesterol acceptors at the luminal side of the enterocyte. Mice were fed a Western-type diet (0.25% wt/wt cholesterol; 16% wt/wt fat), a high-fat diet (no cholesterol; 24% wt/wt fat), or high-cholesterol diet (2% wt/wt), and TICE was measured by isolated intestinal perfusion. Bile salt-phospholipid mixtures served as cholesterol acceptor. Western-type and high-fat diet increased TICE by 50 and 100%, respectively. In contrast, the high-cholesterol diet did not influence TICE. Intestinal scavenger receptor class B type 1 (Sr-B1) mRNA and protein levels correlated with the rate of TICE. Unexpectedly, although confirming a role for Sr-B1, TICE was significantly increased in Sr-B1-deficient mice. Apart from the long-term effect of diets on TICE, acute effects by luminal cholesterol acceptors were also investigated. The phospholipid content of perfusate was the most important regulator of TICE; bile salt concentration or hydrophobicity of bile salts had little effect. In conclusion, TICE can be manipulated by dietary intervention. Specific dietary modifications might provide means to stimulate TICE and, thereby, to enhance total cholesterol turnover.


Author(s):  
Yara Cantika ◽  
Cut Fauziah ◽  
Yuni Setyaningsih

Spermatogenesis can be affected by oxidative stress produced by the increasing of pro-inflammatory adipokines because of high fat diet.The spermatogenesis cells damaged can be prevented with natural substance such as red pitaya (Hylocereus polyrhizus). This study aims to analyze effect of Hylocereus polyrhizus extract on rat’s spermatogenesis cells number that induced by high fat diet. This study had used true-experiment design. 30 rats were divided into 5 groups. Groups 1 to 4 had done treatment for 52 days and group 5 treatment for 104 days. Group 1 Negative control (K1) administered with standard diet, group 2 Positive control (K2) had administered quail egg 10ml/KgBW, group 3 Experiment 1 (P1) had administered quail egg polyrhyzus  10ml/Kg BW and with simvastatin 0,72mg/day, group 4 Experiment 2 (P2) had administered quail egg 10ml/KgBW and wth Hylocereus polyrhizus extract 60mg/day in 52 days, and group 5 Experiment 3 (P3) had administered quail egg 10ml/KgBW and with Hylocereus polyrhizus extract 60mg/day in 104 days. Data were analyzed by One Way ANOVA and continued with Post Hoc Tukey’s HSD (P-Value=0,05) for 52 day groups. Group P1 and P2 showed repairing effect and increasing spermatocytes and spermatids (p.000<0,05) compared to group K2. Group P2 had more spermatids and spermatocytes than group P1 (p.000<0,05). Group P2 52 days’ spermatid cells equalled to group P3 104 days (p.469>0,05). Hylocereus polyrhizus extract not only had mechanism like simvastatin but also contained antioxidant, and a long-term treatment had not proven bad effect to spermatogenesis cells.  Conclusion. Hylocereus polyrhizus extract 60mg/day can repair and increase spermatogenesis cells induced with high fat diet. 


Author(s):  
Xiangyun Liu ◽  
Jiulin Xiang ◽  
Kai Li ◽  
Ru Wang ◽  
Qin Yang

High-fat-diet (HFD) induced BPH mice model used to examine how aerobics exercise prevents the development of BPH and try to find the mechanism. Materials and Methods: C57BL/6J mice were randomized into three groups for a 6-week intervention: Control group (Co, n = 8) and Diet group (Di, n = 8) fed standard diet, and Exercise and diet group fed standard diet meanwhile run on a treadmill at 12m/min, 30 min/day, 6 days/week (Ex+Di, n = 8). Body weight (BW), fat, prostate weight (PW), prostate index (PI), Estradio(E2), Testosterona (T) and estrogen receptor(ER) were detected. Results: The Di had a higher BW, fat, PW and PI, compared to Co and Ex+Di. BW and PI in Ex+Di significantly lower compared to Di, thus running prevented increase in BW and PI. Although, E2 and T in Di and Ex+Di haven’t seen anything statistically significant, compared with Co. However, ERá in Ex+Di (0.039±0.012 ng/ml) was significant reduced (P less than 0.05) compared with Di (0.046±0.011 ng/ml); Compared with Di (0.032±0.009 ng/ml), ERâ in Ex+Di (0.039±0.011 ng/ml) was significant reduced (P less than 0.05). Conclusion: Obesity is an important risk factor for the development of BPH. It may also provide scientific evidence to promote weight loss and aerobic exercise beneficial adjuvant therapies for BPH.


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