Maternal Protein Restriction and Post-Weaning High-Fat Feeding Alter Plasma Amino Acid Profiles and Hepatic Gene Expression in Mice Offspring.
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ABSTRACT:
SUBMITTER: Miyoshi M
PROVIDER: S-EPMC8909731 | biostudies-literature | 2022 Mar
REPOSITORIES: biostudies-literature
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Maternal Protein Restriction and Post-Weaning High-Fat Feeding Alter Plasma Amino Acid Profiles and Hepatic Gene Expression in Mice Offspring.
Miyoshi Moe M Saito Kenji K Jia Huijuan H Kato Hisanori H
Foods (Basel, Switzerland) 20220304 5
Maternal undernutrition during pregnancy is closely associated with epigenetic changes in the child, and it affects the development of obesity throughout the child's life. Here, we investigate the effect of fetal low protein exposure and post-weaning high-fat consumption on plasma amino acid profiles and hepatic gene expression. Mother C57BL/6J mice were fed a 20% (CN) or 9% (LP) casein diet during pregnancy. After birth, the male offspring of both these groups were fed a high-fat diet (HF) from ...[more]
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Project description:In model organisms both the nutrition of the mother and the young offspring could induce long-lasting transcriptional changes in tissues. In livestock, such changes could have important roles in determining nutrient use and meat quality. The main objective was to evaluate if plane of maternal nutrition during late-gestation and weaning age alter the offspring's Longissimus muscle (LM) transcriptome, animal performance, and metabolic hormones. Whole-transcriptome microarray analysis was performed on LM samples of early (EW) and normal weaned (NW) Angus × Simmental calves born to grazing cows receiving no supplement [low plane of nutrition (LPN)] or 2.3 kg high-grain mix/day [medium plane of nutrition (MPN)] during the last 105 days of gestation. Biopsies of LM were harvested at 78 (EW), 187 (NW) and 354 (before slaughter) days of age. Despite greater feed intake in MPN offspring, blood insulin was greater in LPN offspring. Carcass intramuscular fat content was greater in EW offspring. Bioinformatics analysis of the transcriptome highlighted a modest overall response to maternal plane of nutrition, resulting in only 35 differentially expressed genes (DEG). However, weaning age and a high-grain diet (EW) strongly impacted the transcriptome (DEG = 167), especially causing a lipogenic program activation. In addition, between 78 and 187 days of age, EW steers had an activation of the innate immune system due presumably to macrophage infiltration of intramuscular fat. Between 187 and 354 days of age (the "finishing" phase), NW steers had an activation of the lipogenic transcriptome machinery, while EW steers had a clear inhibition through the epigenetic control of histone acetylases. Results underscored the need to conduct further studies to understand better the functional outcome of transcriptome changes induced in the offspring by pre- and post-natal nutrition. Additional knowledge on molecular and functional outcomes would help produce more efficient beef cattle.
| S-EPMC4496061 | biostudies-literature
Project description:Substantial evidence indicated that maternal malnutrition could increase the susceptibility to obesity, insulin resistance, and type 2 diabetes in adulthood. It is increasingly apparent that the brain, especially the hypothalamus, plays a critical role in glucose homeostasis. However, little information is known about the mechanisms linking maternal protein restriction combined with post-weaning high-fat (HF) feeding with altered expression of brain neurotransmitters, and investigations into the epigenetic modifications of hypothalamus in offspring have not been fully elucidated. Our objective was to explore the effects of maternal protein restriction combined with post-weaning HF feeding on glucose metabolism and hypothalamic POMC methylation in male offspring mice. C57/BL6 mice were fed on either low-protein (LP) or normal chow (NC) diet throughout gestation and lactation. Then, the male offspring were randomly weaned to either NC or high-fat (HF) diet until 32 weeks of age. Gene expressions and DNA methylation of hypothalamic proopiomelanocortin (POMC) and melanocortin receptor 4 (MC4R) were determined in male offspring. The results showed that birth weights and body weights at weaning were both significantly lower in male offspring mice of the dams fed with a LP diet. Maternal protein restriction combined with post-weaning high-fat feeding, predisposes higher body weight, persistent glucose intolerance (from weaning to 32 weeks of age), hyperinsulinemia, and hyperleptinemia in male offspring mice. POMC and MC4R expressions were significantly increased in offspring mice fed with maternal LP and postnatal high-fat diet (P < 0.05). Furthermore, maternal protein restriction combined with post-weaning high-fat feeding induced hypomethylation of POMC promoter in the hypothalamus (P < 0.05) and POMC-specific methylation (%) was negatively correlated with the glucose response to a glucose load in male offspring mice (r = -0.42, P = 0.039). In conclusion, maternal LP diet combined with post-weaning high-fat feeding predisposed the male offspring to impaired glucose metabolism and hypothalamic POMC hypomethylation. These findings can advance our thinking about hypothalamic POMC gene methylation between maternal LP diet combined with post-weaning high-fat feeding and metabolic health in offspring.
| S-EPMC8415226 | biostudies-literature
Project description:We evaluated if a higher plane of maternal nutrition during late gestation and weaning age alters the offspring’s Longissimus muscle (LM) transcriptome. A microarray analysis was performed in LM samples of early (EW) and normal weaned (NW) Angus × Simmental calves born from cows that were grazing endophyte-infected tall fescue/red clover pastures with no supplement (low plane of nutrition (LPN)), or supplemented with 2.3 kg of dried distiller’s grains with solubles and soyhulls (70% DDGS/30% soyhulls) (medium plane of nutrition (MPN)) during the last 90 days of gestation. Biopsies were harvested at 78, 187 and 354 days of age. Bioinformatics analysis highlighted that offspring transcriptome did not respond markedly to cow plane of nutrition, resulting in only 13 differentially expressed genes. However, weaning age and a high-starch diet strongly impacted the transcriptome, especially the immediate activation of the lipogenic program in EW steers. In addition, between 78 and 187 days of age, these animals had an activation of the innate immune system due presumably to macrophage infiltration in intramuscular fat. Between 187 and 354 days of age (i.e. the fattening phase), NW steers had an activation of the lipogenic transcriptome machinery, while EW steers had a clear gene transcription inhibition. The latter appears to have occurred through the epigenetic control of histone acetylases, which were down-regulated. Higher cow plane of nutrition alone affected 35 genes in the LM of steers that underscore the presence of a mechanism of macrophage infiltration likely originating from localized oxidative stress as a result of increased levels of hypoplasia and hypertrophy in LM.
2015-02-03 | GSE65560 | GEO
Project description:Background:Maternal malnutrition is a critical factor in determining the risk of obesity and glucose intolerance in offspring. However, little is known about the effects of a maternal high-fat diet (HFD) on the ? cell phenotype in offspring, which is a major factor in glucose homeostasis, especially during the early life of offspring. Methods:Dams were randomly fed a HFD (60% kcal from fat) or a chow diet before pregnancy and during gestation and lactation. Glucose metabolism and the ? cell phenotype were assessed in male offspring at weaning. Results:Dams fed a HFD showed impaired glucose tolerance. A HFD predisposed the offspring to increased impairment of metabolic health, including obesity, glucose intolerance and insulin resistance, compared with offspring from chow diet-fed dams. Furthermore, increased islet sizes and islet densities were observed in male offspring from HFD-fed dams at weaning. There were increases in the insulin-positive area, ? cell mass and ? cell proliferation in male offspring from HFD-fed dams at weaning age. Next, we further determined whether a maternal HFD could affect ? cell apoptosis in mouse offspring and found that there was no significant change in ? cell apoptosis between the HFD and control groups. Conclusion:Our study is novel in showing that a maternal HFD predisposes offspring to impaired glucose metabolism and has a profound effect on ? cell mass and proliferation in offspring mice, which is observed in mice as early as at weaning age. However, further study to clarify the underlying mechanisms is warranted.
| S-EPMC7316079 | biostudies-literature
Project description:Increasing evidence shows that maternal nutrition status has a vital effect on offspring susceptibility to obesity. MicroRNAs are related to lipid metabolism processes. This study aimed to evaluate whether maternal chromium restriction could affect miRNA expression involved in lipid metabolism in offspring. Weaning C57BL/6J mice born from mothers fed with normal control diet or chromium-restricted diet were fed for 13 weeks. The adipose miRNA expression profile was analyzed by miRNA array analysis. At 16 weeks old, pups from dams fed with chromium-restricted diet exhibit higher body weight, fat weight, and serum TC, TG levels. Six miRNAs were identified as upregulated in the RC group compared with the CC group, whereas eight miRNAs were lower than the threshold level set in the RC group. In the validated target genes of these differentially expressed miRNA, the MAPK signaling pathway serves an important role in the influence of early life chromium-restricted diet on lipid metabolism through miRNA. Long-term programming on various specific miRNA and MAPK signaling pathway may be involved in maternal chromium restriction in the adipose of female offspring. Impact statement For the first time, our study demonstrates important miRNA differences in the effect of maternal chromium restriction in offspring. These miRNAs may serve as "bridges" between the mother and the offspring by affecting the MAPK pathway.
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Project description:We evaluated if a higher plane of maternal nutrition during late gestation and weaning age alters the offspringM-bM-^@M-^Ys Longissimus muscle (LM) transcriptome. A microarray analysis was performed in LM samples of early (EW) and normal weaned (NW) Angus M-CM-^W Simmental calves born from cows that were grazing endophyte-infected tall fescue/red clover pastures with no supplement (low plane of nutrition (LPN)), or supplemented with 2.3 kg of dried distillerM-bM-^@M-^Ys grains with solubles and soyhulls (70% DDGS/30% soyhulls) (medium plane of nutrition (MPN)) during the last 90 days of gestation. Biopsies were harvested at 78, 187 and 354 days of age. Bioinformatics analysis highlighted that offspring transcriptome did not respond markedly to cow plane of nutrition, resulting in only 13 differentially expressed genes. However, weaning age and a high-starch diet strongly impacted the transcriptome, especially the immediate activation of the lipogenic program in EW steers. In addition, between 78 and 187 days of age, these animals had an activation of the innate immune system due presumably to macrophage infiltration in intramuscular fat. Between 187 and 354 days of age (i.e. the fattening phase), NW steers had an activation of the lipogenic transcriptome machinery, while EW steers had a clear gene transcription inhibition. The latter appears to have occurred through the epigenetic control of histone acetylases, which were down-regulated. Higher cow plane of nutrition alone affected 35 genes in the LM of steers that underscore the presence of a mechanism of macrophage infiltration likely originating from localized oxidative stress as a result of increased levels of hypoplasia and hypertrophy in LM. A subset of 20 Angus x Simmental beef cows from the University of Illinois Dixon Springs Agriculture Center (DSAC) in Simpson, IL, were selected from a group of animals utilized in a parallel study75. Main effects evaluated were maternal plane of nutrition during late gestation and postnatal management of the offspring. Three months prior to the projected parturition date cows were assigned to treatments (low or medium plane of nutrition) in a split-plot design. Low plane of nutrition (LPN) was achieved by grazing endophyte-infected tall fescue/red clover pastures during July, August, and September with no supplement. Medium plane of nutrition cow diet (MPN) was achieved by grazing endophyte-infected tall fescue/red clover pastures supplemented with 2.3 kg of dried distillerM-bM-^@M-^Ys grains with solubles and soyhulls (70% DDGS/30% soyhulls). Angus x Simmental steer calves were randomly assigned to early or normal weaning treatments within each gestational treatment. This allowed for 10 animals for each postnatal treatment and 5 animals of each of the interactions of gestational M-CM-^W postnatal treatments. At 78 M-BM-1 2 days postpartum, early-wean offspring were weaned, transported to Urbana Beef Unit, and adapted to a high-starch diet until they had ad libitum consumption. At 187 M-BM-1 2 days postpartum, normal-wean offspring were weaned and transported to Urbana Beef Unit. All offspring were co-mingled among treatments. LM biopsies were sampled from a subset of 5 animals per gestational M-CM-^W postnatal treatment at time of early weaning (~78 days) and at time of normal weaning (~187 days), and during the last week prior to harvest (~ 354 days). After normal weaning, all offspring were placed on a common, corn grain-based high-starch finishing diet that is typical of industry management (CP% = 18.1, NDF% = 25.3, ADF% = 14.3, crude fat % = 5.1). All the offspring in the study were harvested at a commercial packing plant when they reached the selected end point target back fat thickness of 1.1 cm. Reported final body weight (BW) was calculated from hot carcass weight using a 62% dressing percentage. In the present study, we used a transcriptome-wide bovine microarray (Agilent-015354 Bovine Oligo Microarray-4x44K) that contains 21,475 unique genes and transcripts of Bos Taurus, with two probes per gene. The methods used for hybridization and scanning were according to manufacturerM-bM-^@M-^Ys protocols and Loor et al45. The microarray data were deposited in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/gds) with accession number GSE-XXXX. GeneSpring GX (Agilent Technologies) was used for data visualization and preliminary data mining. Subsequently, the entire microarray data set with associated statistical P-values were imported into Ingenuity Pathways Analysis M-BM-. (IPA, www.ingenuity.com) in order to examine the number of activated and inhibited differentially expressed genes (DEG). Entrez Gene IDs were used to identify individual sequences. Data from the microarray analysis were normalized for dye and microarray effects (i.e., Lowess normalization and array centering) and used for statistical analysis. The MIXED procedure of SAS (SAS Institute, Inc., Cary, NC, USA) was used for statistical analysis. Fixed effects were treatment (early weaning, normal weaning), diet (low and medium cow plane of nutrition), time (78, 187, and 354 days of age), first, second and third order interactions between diet, time and treatment, and dye (Cy3, Cy5) and random effects included steer and microarray. Raw P values were adjusted using Benjamini and HochbergM-bM-^@M-^Ys false discovery rate (FDR). Bioinformatics analysis of microarray data was performed using DIA 10 and information from the freely-available online databases Kyoto Encyclopedia of Genes and Genomes (KEGG) and Database for Annotation, Visualization, and Integrated Discovery (DAVID) v6.7 databases. A list of gene identifiers (Entrez Gene IDs) was uploaded all at once to extract and summarize functional annotations associated with groups of genes or with each individual gene. The significance value associated with biological processes and pathways is a measure of the likelihood that the distribution of DEG in these pathways and biological processes is due to chance. The significance is expressed as a P-value, which is calculated using the right-tailed Fisher's Exact Test and adjusted using FDR. Details of the DIA approach and its validation have been reported previously. The interpretation of the bioinformatics analysis was performed following the same approach as our previous study.
2015-02-03 | E-GEOD-65560 | biostudies-arrayexpress
Project description:Maternal over- and restricted-feeding during gestation have similar negative consequences for the offspring, including decreased muscularity, increased adiposity, and altered metabolism. Our objective was to determine the effects of poor maternal nutrition during gestation (over- and restricted-feeding) on the offspring muscle metabolite profile. Pregnant ewes (n = 47) were fed 60% (RES), 100% (CON), or 140% (OVER) of NRC requirements starting at day 30.2 ± 0.2 of gestation. Offspring sample collection occurred at days 90 and 135 of gestation, and within 24 h of birth. C2C12 myoblasts were cultured in serum collected from offspring at birth (n = 18; 6 offspring per treatment) for analysis of oxidative and glycolytic capacity. Unbiased metabolite analysis of longissimus muscle samples (n = 72; 8 fetuses per treatment per time point) was performed using mass spectrometry. Data were analyzed by ANOVA for main effects of treatment, time point, and their interaction. Cells cultured in serum from RES offspring exhibited increased proton leak 49% (p = 0.01) compared with CON, but no other variables of mitochondrial respiration or glycolytic function were altered. Mass spectrometry identified 612 metabolites. Principle component analysis identified day of gestation as the primary driver of metabolic change; however, maternal diet also altered the lipid and amino acid profiles in offspring. The abundance of 53 amino acid metabolites and 89 lipid metabolites was altered in RES compared with CON (p ≤ 0.05), including phospholipids, sphingolipids, and ceramides within the lipid metabolism pathway and metabolites involved in glutamate, histidine, and glutathione metabolism. Similarly, abundance of 63 amino acid metabolites and 70 lipid metabolites was altered in OVER compared with CON (p ≤ 0.05). These include metabolites involved in glutamate, histidine, lysine, and tryptophan metabolism and phosphatidylethanolamine, lysophospholipids, and fatty acids involved in lipid metabolism. Further, the amino acid and lipid profiles diverged between RES and OVER, with 69 amino acid and 118 lipid metabolites differing (p ≤ 0.05) between groups. Therefore, maternal diet affects metabolite abundance in offspring longissimus muscle, specifically metabolites involved in lipid and amino metabolism. These changes may impact post-natal skeletal muscle metabolism, possibly altering energy efficiency and long-term health.
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Project description:Maternal obesity and/or high-fat diet during pregnancy predispose the offspring to metabolic disease. It is however unclear how pre-natal and post-natal exposure respectively affect the risk of hepatic steatosis and the trajectory towards non-alcoholic steatohepatitis in the offspring. We investigate hepatic lipid metabolism and how these factors are related to metabolic outcome in new born and young rats. Rat dams were exposed to a high-fat/high sucrose (HFHS) diet for 17 weeks prior to mating and during pregnancy. After birth, female offspring were killed and male offspring were cross-fostered, creating four groups; Control-born pups lactated by control (CC) or HFHS dams (CH) and HFHS-born pups lactated by control (HC) or HFHS dams (HH). At 4 weeks of age, pups were killed and metabolic markers in plasma were assayed, together with hepatic lipid composition and expression of relevant genes. Female HFHS neonates had smaller livers at birth (P < .05), a reduced hepatic lipid content (P < .05) and altered lipid composition. The post-natal environment dominated the metabolic profile in the male offspring at 4 weeks of age. Offspring exposed to a HFHS environment post-natally had increased adiposity (P < .0001), increased hepatic triacylglycrol accumulation (P < .0001), and an altered lipid profile with elevated n-6 polyunsaturated fatty acid (PUFA) levels (P < .0001) and a reduction in ceramide (P < .001) and monounsaturated fatty acid (MUFA) (P < .0001). In summary, maternal HFHS diet during gestation affects the hepatic lipid profile in neonates. The pre-natal exposure becomes less pronounced in young male offspring at 4 weeks of age, where the post-natal diet has the largest impact.
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Project description:Maternal high-fat (HF) diet exposure in utero may affect fetal development and cause metabolic problems throughout life due to lipid dysmetabolism and oxidative damage. Metformin has been suggested as a potential treatment for body weight reduction and nonalcoholic fatty liver disease, but its reprogramming effect on offspring is undetermined. This study assesses the effects of maternal metformin treatment on hepatic steatosis in offspring caused by maternal HF diet. Female rats were fed either a control or an HF diet before conception, with or without metformin treatment during gestation, and placenta and fetal liver tissues were collected. In another experiment, the offspring were fed a control diet until 120 d (adult stage). Metformin treatment during pregnancy ameliorates placental oxidative stress and enhances placental glucose transporter 1 (GLUT1), GLUT3, and GLUT4 expression levels through 5' adenosine monophosphate-activated protein kinase (AMPK) activation. Maternal metformin treatment was shown to reprogram maternal HF diet-induced changes in offspring fatty liver with the effects observed in adulthood as well. Further validation is required to develop maternal metformin therapy for clinical applications.
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Project description:Intrauterine growth restriction (IUGR) leads to the development of metabolic syndrome in adulthood. To explore the potential mechanisms of metabolic imprinting, we investigated the effect of malnutrition in utero on hepatic unfolded protein response (UPR)-related genes in IUGR offspring. An IUGR rat model was developed by feeding a low-protein diet to pregnant rats. The expression levels and activity of hepatic UPR genes were analysed by quantitative PCR (qPCR) arrays and western blotting. The hepatic UPR molecules heat-shock 70-kDa protein 4l (Hspa4l), mitogen-activated protein kinase 10 (Mapk10), and endoplasmic reticulum to nucleus signalling 2 (Ern2) were markedly downregulated in IUGR foetuses, but the expression of Mapk10 and Ern2 returned to normal levels at 3 weeks postnatal. In contrast, cAMP responsive element binding protein 3-like 3 (Creb3l3) was upregulated in hepatic tissues at embryo 20(E20), then restored to normal in adulthood (12 weeks). The protein levels of activating transcription factor 2 (Atf2) and Atf6, two key factors of the UPR pathway, were upregulated in the livers of IUGR foetuses, and the latter remained upregulated until 12 weeks. Combined with our previous findings showing an increase in hepatic gluconeogenesis enzymes in IUGR offspring, we speculated that aberrant intrauterine milieu impaired UPR signalling in hepatic tissues; these alterations early in life might contribute to the predisposition of IUGR foetuses to adult metabolic disorders.
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