DNA Methylation profile in hypothalamus for mouse offspring with maternal high fat (HF), low protein (LP) and control (CO) diets
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE79619 | GEO | 2019/01/01
REPOSITORIES: GEO
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Project description:Early life nutritional imbalances are risk factors for metabolic dysfunctions in adulthood, but the effects of perinatal exposure to high versus low protein diets are poorly understood. We exposed C57BL/6 offspring to a high protein/low carbohydrate (HP/LC) or low protein/high carbohydrate (LP/HC) diet during gestation and lactation, and measured metabolic phenotypes between birth and ten months of age in male offspring. Perinatal HP/LC and LP/HC exposures resulted in a decreased ability to clear glucose in the offspring, with reduced baseline insulin and glucose levels in the LP/HC group and a reduced insulin response post-glucose challenge in the HP/LC group. The LP/HC diet group also showed reduced weight at birth and at weaning age, whereas the HP/LC offspring showed an increased weight at weaning and increased adiposity after 5 months of age. Gene expression profiling of hypothalamic and liver tissues indicated alterations of diverse molecular pathways by both diets. Specifically, hypothalamic transcriptome and pathway analyses indicate perturbations of MAPK and hedgehog signaling, processes associated with neural restructuring and transmission, and phosphate metabolism by perinatal protein imbalances. Liver transcriptome data revealed changes in purine and phosphate metabolism, hedgehog signaling, and circadian rhythm pathways. Our results support that maternal protein imbalances perturb molecular pathways in central and peripheral metabolic tissues and predispose offspring to metabolic dysfunctions.
2018-10-01 | GSE120548 | GEO
Project description:Purpose: Identify the potential effector that might responding to the irritated hypothalamic ER stress as early as postnatal resulting from maternal obesity exposure. Methods: Three-week-old male offspring were selected for extracting RNA sample from the three groups (triplicate in sample): LP (Lg42_P1, Lg63_P2, Lg63_P3), HP (Hg43_P1, Hg43_P2, Hg13_P3) and HA (Hg43_A1, Hg43_A2, Hg13_A3). After standard RNA quantification and qualification, library preparation, clustering, sequencing and quality control, reads were mapped to the reference genome, and quantified of gene expression level with FPKM. The data were further processed for differential expression and other functional analysis. Results: We identified 789 differentially expressed genes (DEGs) (DESeq2, pvalue<0.05, |log2FoldChange|>0.0) in the mice from HP compared with those from LP, of which 408 (52%) were upregulated, while 381 (48%) downregulated. Whereas, for those of HA versus HP, 726 DEGs were detected, with 401 (55%) upregulated and 325 (45%) downregulated. There was a total of 158 overlapped DEGs between the two compared groups. In the following Gene Ontology enrichment analysis, we found that the upregulated DEGs in the HP group were significantly enriched in the categories related to molecular chaperon mediated protein processing. While for those downregulated DEGs in HA, similar theme was enriched with most of the genes from family members of the heat shock protein (Hsp), especially Hsp70. We validated the alteration of two members of Hsp70 in the hypothalamus of the weaning offspring given their crucial role in the stress response. Conclusions: Hspa1b might be the potential effector for the irritated early hypothalamic ER stress and the root of unbalanced stress balance in the hypothalamus undergoing feeding-related circuit axon projection in male offspring from obese dams.
2021-03-05 | GSE162744 | GEO
Project description:A reduction in voluntary feed intake is observed in ruminants consuming nutrient deficient diets, such as those with a low CP or P content, and has been attributed to active metabolic regulation, rather than a physical constraint. The hypothalamus is the key integrator of feed intake regulation in mammals. The objectives of this experiment were to 1) establish a model of metabolic feed intake regulation in ruminants consuming diets of variable CP and P content, and 2) determine key biochemical pathways and influential points of regulation within the hypothalamus. Merino wethers [n = 40; 23.7 ± 1.4 kg liveweight (mean ± SD)] were fed one of five dietary treatments (n = 8/treatment) for 63 days in individual pens. The treatments included targeted combinations of high (H) and low (L) CP (110 and 55 g/kg DM) and high and low P (2.5 and 0.7 g/kg DM) with 9 MJ metabolisable energy (ME) per kg DM which were fed ad libitum (UMEI; unrestricted ME intake) resulting in four experimental diets (HCP-HP-UMEI, LCP-HP-UMEI, HCP-LP-UMEI and LCP-LP-UMEI). An additional nutritional treatment (HCP-HP-RMEI) restricted intake of the HCP-HP diet to an equivalent ME intake of wethers consuming the LCP-LP-UMEI treatment. Wethers offered the LCP-HP-UMEI, HCP-LP-UMEI and LCP-LP-UMEI treatments consumed 42, 32 and 49% less total DM (P ≤ 0.05), respectively than the HCP-HP-UMEI treatment, and this was not attributable to any physical limitation of the rumen. Plasma concentrations of urea nitrogen and inorganic phosphate indicated that these nutrient deficiencies were successfully established. To assess potential mechanisms, RNA-seq was conducted on samples from the arcuate nucleus (ARC), ventromedial hypothalamus and lateral hypothalamus of the wethers, yielding a total of 301, 8 and 148 differentially expressed genes across all pairwise comparisons, respectively. The expression of NPY, AGRP and CARTPT, known for their regulatory role in mammalian feed intake regulation, had a similar transcriptional response in the ARC of wethers consuming nutrient deficient treatments and those consuming a ME restricted treatment, despite these wethers expressing behaviours indicative of satiated and hungry states, respectively. In addition, genes involved with glycolysis (TPI1), the citric acid cycle (CS, OGDH, GLUD1, GOT1) and oxidative phosphorylation (COX5A, ATP5MC1, ATP5F1B, ATP5MC3) were downregulated in the ARC of wethers fed a nutrient deficient (LCP-LP-UMEI) relative to the non-deficient (HCP-HP-UMEI) treatment. In summary, a model for voluntary feed intake restriction was established to determine genome-wide molecular changes in the hypothalamus of young ruminants.
2023-09-12 | GSE221072 | GEO
Project description:The purpose of this study was to identify miRNA that are differentially regulated in the arcuate nucleus of the hypothaamus (ARC) and paraventricular nucleus of the hypothalamus (PVH) after perinatal exposure to maternal obesity.
2024-03-13 | GSE261455 | GEO
Project description:DNA microarray analysis was employed to analyze hepatic gene expression in mice that were protected against HF-induced obesity and liver steatosis (ie HF diets supplemented with lingonberries, blackcurrants or bilberries) and compare to mice who were not protected (HF control) or even experienced increased obesity and fatty liver (HF diet with açai). The study was done to increase understanding of underlying mechanisms of the observed effects.
2015-06-01 | GSE66711 | GEO
Project description:In the present project we examined the effects of maternal obesity to offspring hypothalamic tissue at postnatal day (P) 21. Maternal obesity has emerged as an important risk factor for the development of metabolic disorders in the offspring.To obtain an overview of affected genes in the offsprings hypothalamus, the center of hunger and satiety in the brain, we performed whole genome microarray expression profiling. Female mice were fed either a control diet (SD) or a high fat diet (HFD) after weaning until mating and during pregnancy and gestation. On P21, male pups were sacrificed and blood samples were collected for further analyses. The hypothalamus was cut immediately caudal to the optic chiasm. The dissection was limited laterally by the hypothalamic sulci and dorsally by the mammillothalamic tract. Hypothalamic tissue was immediately frozen at −80° C. A maximum of two offspring per dam were analysed to minimize litter-dependent bias. All studies were performed using male offspring.
2019-08-15 | GSE135830 | GEO
Project description:The microarray experiment was employed to evaluate the gene expressions in skin lesions of LP, hypertrophic LP (HLP), and healthy controls.
2020-01-01 | GSE130403 | GEO
Project description:Early life nutritional imbalances are risk factors for metabolic dysfunctions in adulthood, but the long term effects of perinatal exposure to high versus low protein diets are not completely understood. We exposed C57BL/6J offspring to a high protein/low carbohydrate (HP/LC) or low protein/high carbohydrate (LP/HC) diet during gestation and lactation, and measured metabolic phenotypes between birth and 10 months of age in male offspring. Perinatal HP/LC and LP/HC exposures resulted in a decreased ability to clear glucose in the offspring, with reduced baseline insulin and glucose concentrations in the LP/HC group and a reduced insulin response post-glucose challenge in the HP/LC group. The LP/HC diet group also showed reduced birth and weanling weights, whereas the HP/LC offspring displayed increased weanling weight with increased adiposity beyond 5 months of age. Gene expression profiling of hypothalamus and liver revealed alterations in diverse molecular pathways by both diets. Specifically, hypothalamic transcriptome and pathway analyses demonstrated perturbations of MAPK and hedgehog signaling, processes associated with neural restructuring and transmission, and phosphate metabolism by perinatal protein imbalances. Liver transcriptomics revealed changes in purine and phosphate metabolism, hedgehog signaling, and circadian rhythm pathways. Our results indicate maternal protein imbalances perturbing molecular pathways in central and peripheral metabolic tissues, thereby predisposing the male offspring to metabolic dysfunctions.
| S-EPMC6297185 | biostudies-literature
Project description:Maternal overnutrition during pregnancy/or lactation predisposes offspring obesity and related metabolic syndromes in later life. Hypothalamus is the highest heterogeneous brain region located at the base of the brain that is critical to the regulation of the energy homeostasis.We investigated how the maternal programming shapes the single-nucleus transcriptomic landscapes in postnatal day15 offspring hypothalamus in a sex-specific manner.
2024-02-18 | GSE217677 | GEO
Project description:Changes in miRNA expression in offspring hypothalamus after exposure to maternal obesity
| PRJNA1086988 | ENA