Parental diet affects metabolism, obesity and hypothalamic DNA methylation in Psammomys obesus
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ABSTRACT:
ORGANISM(S): Psammomys obesus
PROVIDER: GSE75483 | GEO | 2016/11/29
SECONDARY ACCESSION(S): PRJNA304410
REPOSITORIES: GEO
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Project description:Though obesity is a global epidemic, the physiological mechanisms involved are little understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT) is nutritionally regulated and 5-HT is a trophic factor, we hypothesized that maternal diet influences fetal 5-HT exposure, which then influences central appetite network development and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant low protein fed rat mothers exhibited elevated serum 5-HT, which was also evident in the placenta and fetal brains at E16.5. This increase was associated with reduced hypothalamic expression of 5-HT2CR - the primary 5-HT receptor influencing appetite. As expected, reduced 5-HT2CR expression was associated with impaired sensitivity to 5-HT-mediated appetite suppression. 5-HT primarily achieves effects on appetite via 5-HT2CR stimulation of pro-opiomelanocortin (POMC) peptides within the arcuate nucleus of the hypothalamus (ARC). We reveal that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC and that 5-HT2AR mRNA is increased in the hypothalamus of in utero growth restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals are more sensitive to 5-HT2AR agonist-induced appetite suppression. These findings may not only reveal a 5-HT-mediated mechanism underlying programming of obesity susceptibility but also provide a promising means to correct it, via a 5-HT2AR agonist treatment. The study was carried out using male Wistar rats (Rattus norvegicus). On postnatal day 3, two experimental groups of offspring were established: controls (offspring of control dams) and recuperated (offspring of dams fed a low-protein diet (8% protein, w/v), but nursed by control dams. The animals were fed with standard chow until 3 months of age where the brains were collected for transcriptomic profiling
2016-02-25 | E-GEOD-76012 | biostudies-arrayexpress
Project description:Adult female Wistar rats (about 220g) obtained from a breeding colony were mated and fed either a protein sufficient (PS) or protein restricted (PR) diet (n = 6 per dietary group) during F0 pregnancy which provided an increase in energy of approximately 25% compared to the diet fed to the breeding colony (2018S). During lactation dams were fed AIN93G and litters were standardisied to 8 offspring within 24 hours of birth with a bias towards females. Offpsring were weaned onto AIN93M at postnatal day 28 and F1 and F2 females were mated on postnatal day 70 (n = 6 per F0 dietary group). F1 and F2 dams were fed the PS diet during pregnancy and AIN93G during lactation. Offspring were weaned onto AIN93M. On postnatal day 70 unmated female offspring were fasted for 12 hours then sacrificed for hepatic transcritpome analysis by microarray. Expression of 1,684 genes differed by at least 2 fold between adult female F1 offspring of F0 dams from both dietary groups. 1680 genes were altered in F2 offspring and 2,065 genes altered in F3 offspring. Expression of 113 genes was altered in all three generations. Of these, 47% showed directionally opposite differences between generations. Gene ontology analysis revealed clear differences in the pathways altered in each generation. F1 and F2 offspring of F0 dams fed a PR diet showed impaired fasting glucose homeostasis. Hepatic phosphoenolpyruvate carboxykinase (PEPCK) expression was elevated in F1 and F2 offspring from F0 PR dams, but decreased in F3, compared to PS offspring
2011-06-01 | E-MEXP-3205 | biostudies-arrayexpress
Project description:Taurine is known to be important for fetal well being and to be able to prevent effects of a low birthweight phenotype when supplemented to pregnant dams. We hypothesized that gestational taurine supplementation would affect gene expression level in 4w offspring liver and skeletal muscle. Pregnant mouse dams were subjected to different diet schemes from day 1 of pregnancy until birth. Pups were killed at 4 weeks of age and liver and quadriceps skeletal muscle taken out and frozen at -80C until analysis. Diet schemes: Normal Protein (20% casein; NP), Normal Protein + taurine (1% taurine supplementation in water ad libitum; NP+tau). The liver and muscle samples were normalized separately.
2010-12-01 | E-GEOD-20577 | biostudies-arrayexpress
Project description:Maternal chromium restriction may disturb susceptibility in offspring. Adipose from maternal chromium diet has 1214 CpG sites that exhibit differential DNA methylationregulated compared to control. We performed DNA methylation array analyses of offspring adipose from chromium restriction dams and control diet dams at 32 week (n=3 per group).
2016-09-08 | E-GEOD-82030 | biostudies-arrayexpress
Project description:Maternal obesity can program metabolic syndrome in offspring but the mechanisms are not well characterized. Moreover, the consequences of maternal overnutrition in the absence of frank obesity remain poorly understood. This study aimed to determine the effects of maternal consumption of a high fat-sucrose diet on the skeletal muscle metabolic and transcriptional profiles of adult offspring. Female Sprague Dawley rats were fed either a diet rich in saturated fat and sucrose (HFD, 23.5% fat, 20% sucrose wt/wt) or a standard chow diet (NFD, 7% fat, 10% sucrose w/w) for the 3 weeks prior to mating and throughout pregnancy and lactation. Although maternal weights were not different between groups at conception or weaning, HFD dams were ~22% heavier than chow fed dams from mid-pregnancy until 4 days post-partum. Adult male offspring of HFD dams were not heavier than controls but demonstrated features of insulin resistance including elevated plasma insulin concentration (+40%, P<0.05). Next Generation mRNA Sequencing was used to identify differentially expressed genes in the soleus muscle of offspring, and Gene Set Enrichment Analysis (GSEA) to detect coordinated changes that are characteristic of a biological function. GSEA identified 15 pathways enriched for up-regulated genes, including cytokine signaling (P<0.005), starch and sucrose metabolism (P<0.017), and inflammatory response (P<0.024). A further 8 pathways were significantly enriched for down-regulated genes including oxidative phosphorylation (P<0.004) and electron transport (P<0.022). Western blots confirmed a ~60% reduction in the phosphorylation of the insulin signaling protein Akt (P<0.05) and ~70% reduction in mitochondrial complexes II (P<0.05) and V expression (P<0.05). On a normal diet, offspring of HFD dams developed an insulin resistant phenotype, with transcriptional evidence of muscle cytokine activation, inflammation and mitochondrial dysfunction. These data indicate that maternal overnutrition, even in the absence of pre-pregnancy obesity can promote metabolic dysregulation and predispose offspring to type 2 diabetes. Messenger RNA profile of skeletal muscle of male offspring from female Sprague Dawley rats fed either a diet rich in saturated fat and sucrose (HFD, 23.5% fat, 20% sucrose wt/wt) or a standard chow diet (NFD, 7% fat, 10% sucrose w/w) for the 3 weeks prior to mating and throughout pregnancy and lactation. There were 5 HFD samples compared to 6 NFD control samples.
2013-08-13 | E-GEOD-49797 | biostudies-arrayexpress
Project description:In utero undernutrition is associated with obesity and insulin resistance, although its effect on skeletal muscle remains poorly defined. We report that, in mice, adult offspring from undernourished dams have decreased energy expenditure, decreased skeletal muscle mitochondrial content, and altered energetics in isolated mitochondria and permeabilized muscle fibers. Strikingly, when these mice are put on a 40% calorie restricted diet they lose half as much weight as calorie restricted controls. Our results reveal for the first time that in utero undernutrition alters metabolic physiology having a profound effect on skeletal muscle energetics and response to calorie restriction in adulthood. We have used a mouse model of low birth weight generated through 50% food restriction of mouse dams during the third week of gestation. We have studied in utero food restricted offspring and control offspring that were not food restricted in utero in both the ad libitum and calorie restricted states. Gene expression profiling was performed on tibialis anterior muscle from 8 mice per group, pooled in pairs.
2014-08-01 | E-GEOD-53520 | biostudies-arrayexpress
Project description:We established a new minimal congenic rat strain containing only a single gene, Zbtb16, from a metabolic syndrome model, the polydactylous rat (PD/Cub) strain, within the spontaneously hypertensive rat (SHR) strain genomic background. 16-week-old SHR and SHR-Zbtb16 rat dams were fed either standard diet during pregnancy and 4 weeks of lactation (control groups) or a high-sucrose diet (HSD, 70% calories as sucrose) during the same period. We have compared the transcriptome profile (GeneChip Rat Gene 2.1 ST Array Strip) in liver, brown and white adipose tissue in adult male offspring of SHR and SHR-Zbtb16 rat dams.
2019-06-28 | E-MTAB-6838 | biostudies-arrayexpress
Project description:Background: Epidemiological studies suggest an association between maternal obesity and adverse neurodevelopmental outcomes in offspring. Objective: To compare the global proteomic portrait in the cerebral cortex between mice born to mothers on a high-fat or control diet who themselves were fed a high-fat or control diet. Methods: Male mice born to dams fed a control (C) or high fat (H) diet four weeks before conception and during gestation and lactation were assigned to either C or H diet at weaning. Mice (n=24) were sacrificed at 19-weeks and their cerebral cortices were pooled into 8 samples and analysed using an iTRAQ based 2D LC-MS methodology. Results: A total of 6,695 proteins were identified and fully quantified (q<0.01). Approximately 10% of these proteins demonstrated a minimum of one Standard Deviation of regulation across all biological replicates in at least one of the experimental groups (CH, HC, HH) relative to the control (CC). Principal component analysis and hierarchical clustering analysis showed that mice clustered based on the diet of the mother and not their current diet. In silico bioinformatics analysis revealed that maternal high-fat diet was significantly associated with response to hypoxia/oxidative stress and apoptosis in the cerebral cortex of the adult offspring. Conclusion: Maternal high-fat diet was associated with distinct endophenotypic changes of the adult mouse cerebral cortex independent of the diet of the offspring. The identified modulated proteins could represent novel therapeutic targets for the prevention of neuropathological features resulting from maternal obesity.
2018-01-29 | PXD001540 | Pride
Project description:Initiation of a vitamin A deficient diet in mid-gestation, maintained in the post-weaning diet is sufficient to cause liver and serum retinoid depletion. Wild type C57Bl/6J timed mated pregnant dams were administered either a defined vitamin A sufficient low fat (12 percent kcal from fat) diet or matched vitamin A deficient diet from embryonic day 10.5. Vitamin A sufficient offspring were weaned onto either a high fat diet (60 percent kcal from fat) or maintained on the low fat 12 percent kcal from fat diet for 11 weeks (14 weeks of age). Gestational vitamin A deficient offspring were maintained on the same vitamin A deficient diet until 14 weeks of age. The impact of the maternal diet on a post-weaning high fat diet was compared to a standard maternal breeder diet followed by the post-weaning high fat diet.
2016-10-12 | GSE87845 | GEO
Project description:Purpose: Study a cohort of C57Bl/6J dams, treated with a control or high-fat-high-sugar diet, and their adult offspring to explore potential hypothalamic mechanisms to explain the link between maternal and offspring obesity. Hypothalamic differential gene expression analysis was conducted following next-generation sequencing (NGS) and analyzed in Ingenuity Pathway Analysis. This methodology was supplementary to in vivo studies which characterized offspring metabolic phenotype. Methods: Total RNA was extracted from a subset of offspring hypothalamus tissue using a RNeasy Mini Kit (Qiagen, Germantown, MD). Tissues were homogenized in RLT buffer using mechanized syringe homogenization. RNA was assessed for purity and concentration using the NanoDrop (NanoDrop Technologies). Approximately 4ug of total RNA was used to generate cDNA by reverse transcription using a cDNA synthesis kit (Applied Biosystems, Carlsbad, CA). Results: There were 31,637 differentially expressed genes in adult OB offspring hypothalamus compared with control diet. Of the identified differentially expressed genes, there were 2510 differentially expressed genes that were significantly different between CON and OB offspring (Supplemental Table 3). In OB offspring, 65% of the identified differentially expressed genes were downregulated whereas 35% were upregulated. Conclusions: Collectively, data demonstrate that maternal obesity without diabetes is associated with adiposity and decreased hypothalamic energy production.
2022-04-13 | GSE200611 | GEO