Diet-Dependent Changes of the DNA Methylome Using a Göttingen Minipig Model for Obesity
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PROVIDER: PRJNA648959 | ENA |
REPOSITORIES: ENA
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Project description:In the present study, we have compared the promoter methylome in liver tissue of a Göttingen minipigs fed a high fat/fructose/cholesterol (FFC) diet with the promotor methylome of GM pigs fed the FFC diet and reverted to standard chow (FFC/SD), and fed standard chow (SD) respectively. Furthermore, we correlated the methylation patterns of key genes with their gene expression profiles in liver. We show that minipigs exhibited extensive, functionally relevant methylome perturbation under FFC diet compared to normal chow group. Also, the methylation levels were highly correlated with gene expression in key genes in the liver. Surprisingly, the diet-induced methylome variation could be only partially reversed to lean stage after replacing the FFC diet to normal chow diet, promotors of several obesity-related genes still remained differential methylated and expression was perturbed even after diet reversion.
2021-02-01 | GSE155197 | GEO
Project description:The underlying mechanism of how the atopic lipids in skeletal muscle affect muscle growth remains elusive. Here we chose miniature Bama swine as our model to mimick human obesity and co-associated metabolic disorders by long time diet induction and study how the atopic fat accumulation in skeletal muscle influence muscle function. After 23 months high-fat high-sucrose diet (HFHSD) fed, the model minipig model of obesity accompanied with metabolic disorders like human, and they had increased body weight and extensive lipids deposition in adipose tissues (AT) and non-AT, especially in skeletal muscle. Further more, the mass of skeletal reduced greatly and the small area (0-2000μm2) muscle reduced after diet induced. The average fiber area of Gastroc reduced 25.2%, but no significant changes appeared in the other skeletal muscles. Antioxidant capacity of skeletal muscle also reduced. Microarray profiles showed genes related to fat deposition promotion (Peroxisome proliferator activated receptor γ, CCAAT/enhancer-binding protein α and apolipoprotein E), muscle growth inhibition (myostatin and p21) up regulated, and some other muscle cell differentiation related genes (myoD) down regulated. Meanwhile, adipokines like adiponectin and 11b-hydroxysteroid dehydrogenase type 1 (11βHSD1) which partake in the crosstalk between AT and skeletal muscles rose up. We draw a clear potential crosstalk pathway that, increased 11βHSD1 secreted by excess AT will promote the expression of the major inhibitor MSTN by activating corticosterone to cortisol, leading to the growth inhibition of skeletal muscle. Overall, this research announces how obesity affects skeletal muscle growth in a crosstalk sight. Male and female Bama minipigs, aged 6 months at the start of the study, were divided into the following two groups for 23 months of treatment. Bama minipigon control (CD group, N=3) were fed standard pig chow. The experimental group (N=6) were fed high-fat high-sucrose diet (53% basal diet, 37% sucrose, 10% lard, HFHSD).
2014-10-15 | E-GEOD-62312 | biostudies-arrayexpress
Project description: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.
| S-EPMC7991730 | biostudies-literature
Project description:The underlying mechanism of how the atopic lipids in skeletal muscle affect muscle growth remains elusive. Here we chose miniature Bama swine as our model to mimick human obesity and co-associated metabolic disorders by long time diet induction and study how the atopic fat accumulation in skeletal muscle influence muscle function. After 23 months high-fat high-sucrose diet (HFHSD) fed, the model minipig model of obesity accompanied with metabolic disorders like human, and they had increased body weight and extensive lipids deposition in adipose tissues (AT) and non-AT, especially in skeletal muscle. Further more, the mass of skeletal reduced greatly and the small area (0-2000μm2) muscle reduced after diet induced. The average fiber area of Gastroc reduced 25.2%, but no significant changes appeared in the other skeletal muscles. Antioxidant capacity of skeletal muscle also reduced. Microarray profiles showed genes related to fat deposition promotion (Peroxisome proliferator activated receptor γ, CCAAT/enhancer-binding protein α and apolipoprotein E), muscle growth inhibition (myostatin and p21) up regulated, and some other muscle cell differentiation related genes (myoD) down regulated. Meanwhile, adipokines like adiponectin and 11b-hydroxysteroid dehydrogenase type 1 (11βHSD1) which partake in the crosstalk between AT and skeletal muscles rose up. We draw a clear potential crosstalk pathway that, increased 11βHSD1 secreted by excess AT will promote the expression of the major inhibitor MSTN by activating corticosterone to cortisol, leading to the growth inhibition of skeletal muscle. Overall, this research announces how obesity affects skeletal muscle growth in a crosstalk sight.
2014-10-15 | GSE62312 | GEO
Project description:Male Göttingen Minipigs were divided into 4 groups: SD (standard diet, n=8), FFC (FFC diet, n=16), FFC-DIA (FFC diet + diabetes, n=14), FFC-DIA+S (FFC diet with extra salt + diabetes, n=14). Blood and urine biomarkers, glomerular filtration rate (GFR), blood pressure and resistive index (RI) were evaluated after 6-7 months (T1) and 12-13 months (T2). Histology, electron microscopy and gene expression (excluding FFC-DIA+S) were evaluated at T2. Göttingen Minipigs fed FFC diet displayed some of the characteristic features of human ORG. Presence of diabetes on top of FFC diet, lead to changes resembling the early phases of human DN.
2023-04-19 | GSE215843 | GEO
Project description:The Göttingen Minipig is gaining ground as nonrodent species in safety testing of drugs for pediatric indications. Due to developmental changes in pharmacokinetics (PK) and pharmacodynamics (PD), physiologically-based pharmacokinetic (PBPK) models are built to better predict drug exposure in children and to aid species selection for nonclinical safety studies. These PBPK models require high quality physiological and PK/PD data such as protein abundance of drug metabolizing enzymes. These data are available for man and rat, but scarce for the Göttingen Minipig. The aim of this study was to assess hepatic cytochrome P450 (CYP) protein abundance in the developing Göttingen Minipig by using mass spectrometry. In addition, sex-related differences in CYP protein abundance and correlation of CYP enzyme activity with CYP protein abundance were assessed. The following age groups were included: gestational day (GD) 84 - 86 (n = 8), GD 108 (n = 6), postnatal day (PND) 1 (n = 8), PND 3 (n = 8), PND 7 (n = 8), PND 28 (n = 8) and adult (n = 8). Liver microsomes were extracted and protein abundance was compared to that in adult animals. Next, the CYP protein abundance was correlated to CYP enzyme activity in the same biological samples. In general, CYP protein abundance gradually increased during development. However, we observed a stable protein expression over time for CYP4A24 and CYP20A1 and for CYP51A1, a high protein expression during the fetal stages was followed by a decrease during the first month of life and an increase towards adulthood. Sex-related differences were observed for CYP4V2_2a and CYP20A1 at PND 1 with highest expression in females for both isoforms. In the adult samples, sex-related differences were detected for CYP1A1, CYP1A2, CYP2A19, CYP2E1_2, CYP3A22, CYP4V2_2a and CYP4V2_2b with higher values in female compared to male Göttingen Minipigs. The correlation analysis between CYP protein abundance and CYP enzyme activity showed that CYP3A22 protein abundance correlated clearly with the metabolism of midazolam at PND 7. These data are remarkably comparable to human data and provide a valuable step forward in the construction of a neonatal and juvenile Göttingen Minipig PBPK model.
2021-02-26 | PXD024158 | Pride
Project description:The purpose of this experiment was to determine the murine liver expression traits that were changed in response to diet induced obesity. Keywords: diet induced obesity signature
2007-02-17 | GSE7028 | GEO
Project description:The experimental goals of this study were to determine differences in adipose tissue gene expression in genetically identical mice that have variability in their susceptibility towards diet-induced obesity following 4 weeks feeding a high saturated fat diet. Keywords: comparative gene expression analysis
2006-04-28 | GSE4692 | GEO
Project description:Diet induced obesity in rat was associated with myocardial dysfunction, hypertension and fibrosis. This study aimed to explore microRNA expression profiles in diet obesity-induced rat myocardium. Wistar rats were feed normal chow or high-fat diet for 20 weeks. After that, cardiac function was evaluated by echocardiography. Left ventricular myocardium was harvest to assess the extent of hypertension and fibrosis, meanwile, the left ventricular microRNA expression was analyzed using Agilent Rat miRNA microarray. Significant cardiac dysfunction, hypertension and fibrosis were found in diet-induced obesity rats as compared with normal diet rats. rno-miR-141-3p and rno-miR-144-3p were also significantly increased in myocardium of diet-induced obesity rat. These findings suggest that specific miRNA differences may contribute to the alteration in cardiac function, hypertension and fibrosis which responses to diet-induced obesity.
2020-01-07 | GSE143168 | GEO
Project description:The role of diet composition in high-fat diet induced obesity related microbiota composition.
| PRJEB22352 | ENA