Breast Milk MicroRNAs Related to Leptin and Adiponectin Function Can Be Modulated by Maternal Diet and Influence Offspring Phenotype in Rats.
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ABSTRACT:
SUBMITTER: Alonso-Bernaldez M
PROVIDER: S-EPMC9266562 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Human milk microorganisms contribute not only to the healthy development of the immune system in infants, but also in shaping the gut microbiota. We evaluated the effect of the maternal diet during pregnancy and during the first month of lactation on the human milk microbiota in a cross-sectional study including 94 healthy lactating women. Microbiota composition was determined by 16S rDNA profiling and nutrient intake assessed through food questionnaires. Thirteen genera were present in at least 90% of all samples, with three genera present in all samples: Streptococcus, Staphylococcus, and Corynebacterium. Cluster analysis indicated two distinct compositions: one marked by a high abundance of Streptococcus (cluster 1), and other by a high abundance of Staphylococcus (cluster 2). A global association with milk microbiota diversity was observed for vitamin C intake during pregnancy (p = 0.029), which was higher for cluster 2 individuals (cluster 2 median = 232 mg/d; cluster 1 = 175 mg/d; p = 0.02). Positive correlations were found between Bifidobacterium in the milk and intake of polyunsaturated and linoleic fatty acids during the lactation period (p < 0.01). We show that maternal diet influences the human milk microbiota, especially during pregnancy, which may contribute in shaping the gut microbiota.
| S-EPMC6920866 | biostudies-literature
Project description:A maternal diet that is low in protein increases the susceptibility of offspring to type 2 diabetes by inducing long-term alterations in ? cell mass and function. Nutrients and growth factor signaling converge through mTOR, suggesting that this pathway participates in ? cell programming during fetal development. Here, we revealed that newborns of dams exposed to low-protein diet (LP0.5) throughout pregnancy exhibited decreased insulin levels, a lower ? cell fraction, and reduced mTOR signaling. Adult offspring of LP0.5-exposed mothers exhibited glucose intolerance as a result of an insulin secretory defect and not ? cell mass reduction. The ? cell insulin secretory defect was distal to glucose-dependent Ca2+ influx and resulted from reduced proinsulin biosynthesis and insulin content. Islets from offspring of LP0.5-fed dams exhibited reduced mTOR and increased expression of a subset of microRNAs, and blockade of microRNA-199a-3p and -342 in these islets restored mTOR and insulin secretion to normal. Finally, transient ? cell activation of mTORC1 signaling in offspring during the last week of pregnancy of mothers fed a LP0.5 rescued the defect in the neonatal ? cell fraction and metabolic abnormalities in the adult. Together, these findings indicate that a maternal low-protein diet alters microRNA and mTOR expression in the offspring, influencing insulin secretion and glucose homeostasis.
| S-EPMC4191023 | biostudies-literature
Project description:ObjectiveObesity in pregnancy significantly increases the risk of the offspring developing obesity after birth. The aims of this study were to test the hypothesis that maternal obesity increases oxidative stress during fetal development, and to determine whether administration of an antioxidant supplement to pregnant Western diet-fed rats would prevent the development of adiposity in the offspring.Research design and methodsFemale Sprague Dawley rats were started on the designated diet at 4 weeks of age. Four groups of animals were studied: control chow (control); control + antioxidants (control+Aox); Western diet (Western); and Western diet + antioxidants (Western+Aox). The rats were mated at 12 to 14 weeks of age, and all pups were weaned onto control diet.ResultsOffspring from dams fed the Western diet had significantly increased adiposity as early as 2 weeks of age as well as impaired glucose tolerance compared with offspring of dams fed a control diet. Inflammation and oxidative stress were increased in preimplantation embryos, fetuses, and newborns of Western diet-fed rats. Gene expression of proadipogenic and lipogenic genes was altered in fat tissue of rats at 2 weeks and 2 months of age. The addition of an antioxidant supplement decreased adiposity and normalized glucose tolerance. CONCLUSIONS; Inflammation and oxidative stress appear to play a key role in the development of increased adiposity in the offspring of Western diet-fed pregnant dams. Restoration of the antioxidant balance during pregnancy in the Western diet-fed dam is associated with decreased adiposity in offspring.
| S-EPMC2992766 | biostudies-literature
Project description:There is emerging evidence that non-coding RNAs (ncRNAs) within maternal breast milk (MBM) impart unique metabolic and immunologic effects on developing infants. Most studies examining ncRNAs in MBM have focused on microRNAs. It remains unclear whether microRNA levels are related to other ncRNAs, or whether they are impacted by maternal characteristics. This longitudinal cohort study examined 503 MBM samples from 192 mothers to: 1) identify the most abundant ncRNAs in MBM; 2) examine the impact of milk maturity on ncRNAs; and 3) determine whether maternal characteristics affect ncRNAs. MBM was collected at 0, 1, and 4 months post-delivery. High throughput sequencing quantified ncRNAs within the lipid fraction. There were 3069 ncRNAs and 238 microRNAs with consistent MBM presence (≥10 reads in ≥10% samples). Levels of 17 ncRNAs and 11 microRNAs accounted for 80% of the total RNA content. Most abundant microRNAs displayed relationships ([R]>0.2, adj p< 0.05) with abundant ncRNAs. A large proportion of ncRNAs (1269/3069; 41%) and microRNAs (206/238; 86%) were affected by MBM maturity. The majority of microRNAs (111/206; 54%) increased from 0-4 months. Few ncRNAs and microRNAs were affected (adj p < 0.05) by maternal age, race, parity, body mass index, gestational diabetes, or collection time. However, nearly half of abundant microRNAs (4/11) were impacted by diet. To our knowledge this is the largest study of MBM ncRNAs, and the first to demonstrate a relationship between MBM microRNAs and maternal diet. Such knowledge could guide nutritional interventions aimed at optimizing metabolic and immunologic microRNA profiles within MBM.
| S-EPMC8796169 | biostudies-literature
Project description:Gestational exposure to maternal overweight (OW) influences the risk of obesity in adult life. Male offspring from OW dams gain greater body weight and fat mass and develop insulin resistance when fed high-fat diets (45% fat). In this report, we identify molecular targets of maternal OW-induced programming at postnatal d 21 before challenge with the high-fat diet. We conducted global transcriptome profiling, gene/protein expression analyses, and characterization of downstream signaling of insulin and adiponectin pathways in conjunction with endocrine and biochemical characterization. Offspring born to OW dams displayed increased serum insulin, leptin, and resistin levels (P < 0.05) at postnatal d 21 preceding changes in body composition. A lipogenic transcriptome signature in the liver, before development of obesity, was evident in OW-dam offspring. A coordinated locus of 20 sterol regulatory element-binding protein-1-regulated target genes was induced by maternal OW. Increased nuclear levels of sterol regulatory element-binding protein-1 and recruitment to the fatty acid synthase promoter were confirmed via ELISA and chromatin immunoprecipitation analyses, respectively. Higher fatty acid synthase and acetyl coenzyme A carboxylase protein and pAKT (Thr(308)) and phospho-insulin receptor-beta were confirmed via immunoblotting. Maternal OW also attenuated AMP kinase/peroxisome proliferator-activated receptor-alpha signaling in the offspring liver, including transcriptional down-regulation of several peroxisome proliferator-activated receptor-alpha-regulated genes. Hepatic mRNA and circulating fibroblast growth factor-21 levels were significantly lower in OW-dam offspring. Furthermore, serum levels of high-molecular-weight adiponectin (P < 0.05) were decreased in OW-dam offspring. Phosphorylation of hepatic AMP-kinase (Thr(172)) was significantly decreased in OW-dam offspring, along with lower AdipoR1 mRNA. Our results strongly suggest that gestational exposure to maternal obesity programs multiple aspects of energy-balance regulation in the offspring.
| S-EPMC2875830 | biostudies-other
Project description:Overnutrition in pregnancy and lactation affects fetal and early postnatal development, which can result in metabolic disorders in adulthood. We tested a hypothesis that variation of the Zbtb16 gene, a significant energy metabolism regulator, modulates the effect of maternal high-sucrose diet (HSD) on metabolic and transcriptomic profiles of the offspring. We used the spontaneously hypertensive rat (SHR) strain and a minimal congenic rat strain SHR-Zbtb16, carrying the Zbtb16 gene allele originating from the PD/Cub rat, a metabolic syndrome model. Sixteen-week-old SHR and SHR-Zbtb16 rat dams were fed either standard diet (control groups) or a high-sucrose diet (HSD, 70% calories as sucrose) during pregnancy and 4 weeks of lactation. In dams of both strains, we observed an HSD-induced increase of cholesterol and triacylglycerol concentrations in VLDL particles and a decrease of cholesterol and triacylglycerols content in medium to very small LDL particles. In male offspring, exposure to maternal HSD substantially increased brown fat weight in both strains, decreased triglycerides in LDL particles, and impaired glucose tolerance exclusively in SHR. The transcriptome assessment revealed networks of transcripts reflecting the shifts induced by maternal HSD with major nodes including mir-126, Hsd11b1 in the brown adipose tissue, Pcsk9, Nr0b2 in the liver and Hsd11b1, Slc2a4 in white adipose tissue. In summary, maternal HSD feeding during pregnancy and lactation affected brown fat deposition and lipid metabolism in adult male offspring and induced major transcriptome shifts in liver, white, and brown adipose tissues. The Zbtb16 variation present in the SHR-Zbtb16 led to several strain-specific effects of the maternal HSD, particularly the transcriptomic profile shifts of the adult male offspring.
| S-EPMC7518089 | biostudies-literature
Project description:Breast milk constitutes a dietary source of leptin, adiponectin and microRNAs (miRNAs) for newborns. Expression of miRNAs previously associated with maternal obesity, leptin or adiponectin function were assessed and their impact on infant weight analyzed. Milk samples were collected (at month 1, 2, and 3) from a cohort of 59 healthy lactating mothers (38 normal-weight and 21 overweight/obese (BMI ? 25)), and infant growth was followed up to 2 years of age. Thirteen miRNAs, leptin and adiponectin were determined in milk. Leptin, adiponectin and miRNA showed a decrease over time of lactation in normal-weight mothers that was altered in overweight/obesity. Furthermore, negative correlations were observed in normal-weight mothers between the expression of miRNAs in milk and the concentration of leptin or adiponectin, but were absent in overweight/obesity. Moreover, miRNAs negatively correlated with infant BMI only in normal-weight mothers (miR-103, miR-17, miR-181a, miR-222, miR-let7c and miR-146b). Interestingly, target genes of milk miRNAs differently regulated in overweight/obesity could be related to neurodevelopmental processes. In conclusion, a set of miRNAs present in breast milk, in close conjunction with leptin and adiponectin, are natural bioactive compounds with the potential to modulate infant growth and brain development, an interplay that is disturbed in the case of maternal overweight/obesity.
| S-EPMC6893542 | biostudies-literature
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:BackgroundMaternal diet is an important factor in prenatal development that also has implications for disease risk later in life. The adipokine leptin is a key regulator of energy homeostasis and may be involved in the association between maternal nutrition, maternal obesity, and infant outcomes. DNA methylation of placenta genes may occur in response to exposures and may program subsequent infant development. This study examined maternal diet, placenta leptin gene DNA methylation, and neonatal growth in a sample of healthy neonates and their mothers.MethodsMothers and their healthy neonates (N = 135) were recruited within 1-2 days following delivery at Women and Infants Hospital in Providence, RI. A structured interview was conducted to assess maternal dietary intake. Maternal pre-pregnancy weight, weight gain during pregnancy, maternal health, medications, and vitamin use were obtained from medical records. Bisulfite pyrosequencing was used to measure methylation of CpG sites in the promoter region of the placenta leptin gene and determine genotype of the leptin single nucleotide polymorphism (SNP) rs2167270, which is known to influence leptin methylation. Bivariate analyses and linear regression models were used to evaluate associations of demographics, diet, and mean leptin methylation.ResultsGenotype was a significant predictor of placenta leptin DNA methylation (p < .01), and after controlling for this and other relevant maternal and infant covariates, lower levels of leptin methylation were significantly associated with greater intake of carbohydrates (p < .05), in particular added sugars (p < .05) and white/refined carbohydrates (p < .05). Total caloric intake was also associated with placenta leptin methylation (p < .05), however after controlling for relevant covariates, significance diminished to trend-level. There were no significant associations of placenta leptin methylation and intake of protein (p > .05) or fat (p > .05).ConclusionThese findings underline the importance of intake of carbohydrate consumption for methylation of the placenta leptin gene. Because methylation reduces gene transcription, lower methylation may indicate a placenta response to high caloric intake and carbohydrate food that would result in higher levels of this hormone during fetal development. Further investigation of the developmental ramifications of epigenetic changes to placenta leptin methylation should be pursued.
| S-EPMC7185035 | biostudies-literature
Project description:Lactation is a critical period during which maternal sub- or over-nutrition affect milk composition and offspring development that can have lasting health effects. The consequences of moderate high-fat, high-simple carbohydrate diet (WD) consumption by rat dams, during gestation and lactation, on milk composition and offspring blood lipidome and its growth, at weaning, were investigated by using a comprehensive lipidomic study on mass-spectrometric platform combined to targeted fatty- and free amino-acids analysis. This holistic approach allowed clear-cut differences in mature milk-lipidomic signature according to maternal diet with a similar content of protein, lactose and leptin. The lower WD-milk content in total fat and triglycerides (TGs), particularly in TGs-with saturated medium-chain, and higher levels in both sphingolipid (SL) and TG species with unsaturated long-chain were associated to a specific offspring blood-lipidome with decreased levels in TGs-containing saturated fatty acid (FA). The sexual-dimorphism in the FA-distribution in TG (higher TGs-rich in oleic and linoleic acids, specifically in males) and SL species (increased levels in very long-chain ceramides, specifically in females) could be associated with some differences that we observed between males and females like a higher total body weight gain in females and an increased preference for fatty taste in males upon weaning.
| S-EPMC7432416 | biostudies-literature