Project description:Decreased fetal nutrient delivery is a major cause of developmental neuropathology. Although intrauterine growth restriction spares fetal brain weight, we hypothesized that frontal cortices of fetuses of mothers nutrient restricted during pregnancy, would have decreased ribosomal protein expression. This could potentially result in compromised function since these cellular subunits play a central role in protein synthesis and cellular energetics. Fetal baboons from mothers fed as ad lib controls (CTR) or globally nutrient restricted (MNR) by 30% from 30 - 165 days of gestation (term ~ 184 days in length) were studied. At necropsy, the average body weight of CTR mothers had increased by 11.3% while that of MNR mothers had decreased by 5.5% from before pregnancy. Body weights of MNR fetuses were 17% smaller than CTR fetal weights, but fetal brains were not different. As measured by gene array, 24 of 75 ribosomal protein mRNAs detected were decreased. Protein expression of 7 of 8 ribosomal proteins, assessed by semi-quantitative immunohistochemistry, was significantly (p< 0.05) or marginally (p > 0.05 < 0.1) decreased. The brains of growth-restricted fetuses are often assumed to be normal because of brain growth sparing. However, the present findings regarding ribosomal protein expression, strongly suggest that nutrient restriction in pregnancy, regardless of cause, inhibits protein synthesis in the fetal brain. In addition, these effects may be exacerbated if continued postnatally with possible effects on important protein dependent processes such as long-term memory storage.
Project description:Maternal obesity programs the offspring to cardiovascular disease, insulin resistance, and obesity. We sequenced and profiled the cardiac miRNAs that were dysregulated in the hearts of baboon fetuses born to a high fat / high fructose diet fed mothers compared to a regular diet fed mothers. Fetal hearts were collected from baboon fetuses born to obese and lean mothers, total RNA was isolated, and fetal cardiac miRNA were sequenced and profiled
Project description:DNA methylation profiles of the livers of 1 day old rats from mothers fed with three different diets during gestation. The first animal group was fed with a normal diet (c=control); second group received much less protein than normal and slighlty more carbs (p=low protein, or programmed); third group diet was same as low protein but with extra folic acid (f=low protein+folate). All diets were matched for energy.
Project description:Quantification of acetylation stoichiometry from mitochondrial enriched proteins from mouse livers. Conditions compared include genotype, diet, and age; i.e. Sirt3 KO vs Sirt3 WT, caloric restricted (CR) diet vs control diet (CD), and 5 months old vs 25 months old.
Project description:RNA-sequening of livers from male and female C57BL/6J mice fed either chow diet or chow diet + simvastatin (0.1g/kg body weight) for 4 weeks.
Project description:A comparison of the liver transcriptomes of 1 day old rats that are born to mothers fed with three different diets during gestation. The first animal group was fed with a normal diet (control); second group received much less protein than normal and slightly more carbs (low protein); third group diet was same as low protein but with an extra dosage of folic acid (lowp.+f). All diets were matched for energy. Total RNA was extracted from rat livers of 4 offsprings per animal group (4 biological replicates x group)
Project description:DNA methylation profiles of the livers of 1 day old rats from mothers fed with three different diets during gestation. The first animal group was fed with a normal diet (c=control); second group received much less protein than normal and slighlty more carbs (p=low protein, or programmed); third group diet was same as low protein but with extra folic acid (f=low protein+folate). All diets were matched for energy. Genomic DNA from rat livers was subjected to selection according to the methyl-CpG binding domain-based (MBD) protein protocol (DNA pooled from 6 individuals per group) and the resulting fragments sequenced in high throughput. Methylated DNA was captured with MethylCap kit (Diagenode). Approximately 10 ng of captured DNA was used for library preparation (ChIP-seq DNA sample Prep Kit, Illumina).
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
Project description:1. White adipose tissues (WAT) are capable of secreting not only fatty acids but also a class of secretory proteins that modulate the homeostasis of distant organs, including the liver. To identify potential WAT-enriched secretory factors involved in NASH progression, C57BL/6 male mice were fed with a normal chow diet or HFHC diet for two different periods: 12 weeks and 28 weeks. Then, we compared the expression profile of epididymal WAT (eWAT) from mouse models of NAFL and NASH above mentioned by RNA-Sequencing analysis. 2. To investigate the contribution of Sparcl1 in the pathogenesis of NASH, male C57BL/6J mice were fed a HFHC diet for 12 weeks, and then intraperitoneal injected with saline or recombinant Sparcl1 protein (0.2mg/kg) every other day for 3 weeks. To elucidate the molecular basis of Sparcl1-mediated NASH progression, we conducted RNA-Sequencing analysis for differentially expressed genes using the livers of chronic recombinant Sparcl1 protein or saline- treated mice.
Project description:We used microarrays to determine the transcriptional profiles of placental tissue obtained from women who smoked during pregnancy and from women who did not smoke during pregnancy. Fetal growth restriction is a frequent complication in mothers who smoke cigarettes during pregnancy. To evaluate novel pathways that regulate fetal growth affected by mothers who smoke, we isolated placental mRNA from smoking mothers with severe fetal growth restriction and compared them by microarray analysis to non-smoking mothers with appropriately grown fetuses. Bioinformatics analysis revealed distinct transcriptional patterns in the placentas of smoking mothers when compared to placentas from control non-smoking women. Analyses of the top upregulated and downregulated genes revealed several gene products such as secreted frizzled related protein 1 that was markedly upregulated in the placentas from women who smoked cigarettes during pregnancy.