Maternal Inactivity Programs Skeletal Muscle Dysfunction in Offspring Mice by Attenuating Apelin Signaling and Mitochondrial Biogenesis.
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ABSTRACT:
SUBMITTER: Son JS
PROVIDER: S-EPMC8137280 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The obesity rate is rapidly increasing, which has been attributed to lack of exercise and excessive energy intake. Here, we found a previously unidentified explanation, due to lack of maternal exercise. In this study, healthy maternal mice were assigned either to a sedentary lifestyle or to exercise daily, and fetal brown adipose tissue (BAT) development and offspring metabolic health were analyzed. Compared to the sedentary group, maternal exercise enhanced DNA demethylation of Prdm16 promoter and BAT development and prevented obesity of offspring when challenged with a high-energy diet. Apelin, an exerkine, was elevated in both maternal and fetal circulations due to exercise, and maternal administration of apelin mimicked the beneficial effects of exercise on fetal BAT development and offspring metabolic health. Together, maternal exercise enhances thermogenesis and the metabolic health of offspring mice, suggesting that the sedentary lifestyle during pregnancy contributes to the obesity epidemic in modern societies.
| S-EPMC7164955 | biostudies-literature
Project description:Understanding the link between mother's obesity and regulation of the child's appetite is a prerequisite for the design of successful preventive strategies. Beyond the possible contributions of genetic heritage, family culture, and hormonal and metabolic environment during pregnancy, we investigate in the present paper the causal role of the transmission of the maternal microbiotas in obesity as microbiotas differ between lean and obese mothers, maternal microbiotas are the main determinants of a baby's gut colonization, and the intestinal microbiota resulting from the early colonization could impact the feeding behavior of the offspring with short- and long-term consequences on body weight. We thus investigated the potential role of vertical transfers of maternal microbiotas in programming the eating behavior of the offspring. Selectively bred obese-prone (OP)/obese-resistant (OR) Sprague-Dawley dams were used since differences in the cecal microbiota have been evidenced from males of that strain. Microbiota collected from vagina (at the end of gestation), feces, and milk (at postnatal days 1, 5, 10, and 15) of OP/OR dams were orally inoculated to conventional Fischer F344 recipient pups from birth to 15 days of age to create three groups of pups: F-OP, F-OR, and F-Sham group (that received the vehicle). We first checked microbiotal differences between inoculas. We then assessed the impact of transfer (from birth to adulthood) onto the intestinal microbiota of recipients rats, their growth, and their eating behavior by measuring their caloric intake, their anticipatory food reward responses, their preference for sweet and fat tastes in solutions, and the sensations that extend after food ingestion. Finally, we searched for correlation between microbiota composition and food intake parameters. We found that maternal transfer of microbiota differing in composition led to alterations in pups' gut microbiota composition that did not last until adulthood but were associated with specific eating behavior characteristics that were predisposing F-OP rats to higher risk of over consuming at subsequent periods of their life. These findings support the view that neonatal gut microbiotal transfer can program eating behavior, even without a significant long-lasting impact on adulthood microbiota composition.
| S-EPMC8239415 | biostudies-literature
Project description:The intrauterine environment is a major contributor to increased rates of metabolic disease in adults. Intrahepatic cholestasis of pregnancy (ICP) is a liver disease of pregnancy that affects 0.5%-2% of pregnant women and is characterized by increased bile acid levels in the maternal serum. The influence of ICP on the metabolic health of offspring is unknown. We analyzed the Northern Finland birth cohort 1985-1986 database and found that 16-year-old children of mothers with ICP had altered lipid profiles. Males had increased BMI, and females exhibited increased waist and hip girth compared with the offspring of uncomplicated pregnancies. We further investigated the effect of maternal cholestasis on the metabolism of adult offspring in the mouse. Females from cholestatic mothers developed a severe obese, diabetic phenotype with hepatosteatosis following a Western diet, whereas matched mice not exposed to cholestasis in utero did not. Female littermates were susceptible to metabolic disease before dietary challenge. Human and mouse studies showed an accumulation of lipids in the fetoplacental unit and increased transplacental cholesterol transport in cholestatic pregnancy. We believe this is the first report showing that cholestatic pregnancy in the absence of altered maternal BMI or diabetes can program metabolic disease in the offspring.
| S-EPMC3696570 | biostudies-other
Project description:The molecular mechanisms underlying the response to exercise and inactivity are not fully understood. We propose an innovative approach to profile the skeletal muscle transcriptome to exercise and inactivity using 66 published datasets. Data collected from human studies of aerobic and resistance exercise, including acute and chronic exercise training, were integrated using meta-analysis methods (www.metamex.eu). Here we use gene ontology and pathway analyses to reveal selective pathways activated by inactivity, aerobic versus resistance and acute versus chronic exercise training. We identify NR4A3 as one of the most exercise- and inactivity-responsive genes, and establish a role for this nuclear receptor in mediating the metabolic responses to exercise-like stimuli in vitro. The meta-analysis (MetaMEx) also highlights the differential response to exercise in individuals with metabolic impairments. MetaMEx provides the most extensive dataset of skeletal muscle transcriptional responses to different modes of exercise and an online interface to readily interrogate the database.
| S-EPMC6981202 | biostudies-literature
Project description:A maternal high-fat (HF) diet during pregnancy can lead to metabolic compromise, such as insulin resistance in adult offspring. Skeletal muscle mitochondrial dysfunction is one mechanism contributing to metabolic impairments in insulin resistant states. Therefore, the present study aimed to investigate whether mitochondrial dysfunction is evident in metabolically compromised offspring born to HF-fed dams. Sprague-Dawley dams were randomly assigned to receive a purified control diet (CD; 10% kcal from fat) or a high fat diet (HFD; 45% kcal from fat) for 10 days prior to mating, throughout pregnancy and during lactation. From weaning, all male offspring received a standard chow diet and soleus muscle was collected at day 150. Expression of the mitochondrial transcription factors nuclear respiratory factor-1 (NRF1) and mitochondrial transcription factor A (mtTFA) were downregulated in HF offspring. Furthermore, genes encoding the mitochondrial electron transport system (ETS) respiratory complex subunits were suppressed in HF offspring. Moreover, protein expression of the complex I subunit, NDUFB8, was downregulated in HF offspring (36%), which was paralleled by decreased maximal catalytic linked activity of complex I and III (40%). Together, these results indicate that exposure to a maternal HF diet during development may elicit lifelong mitochondrial alterations in offspring skeletal muscle.
| S-EPMC5114294 | biostudies-literature
Project description:ObjectiveThe effects of maternal undernutrition during midgestation on muscle fiber histology, myosin heavy chain (MyHC) expression, methylation modification of myogenic factors, and the mammalian target of rapamycin (mTOR) signaling pathway in the skeletal muscles of prenatal and postnatal goats were examined.MethodsTwenty-four pregnant goats were assigned to a control (100% of the nutrients requirement, n = 12) or a restricted group (60% of the nutrients requirement, n = 12) between 45 and 100 days of gestation. Descendants were harvested at day 100 of gestation and at day 90 after birth to collect the femoris muscle tissue.ResultsMaternal undernutrition increased (p<0.05) the fiber area of the vastus muscle in the fetuses and enhanced (p<0.01) the proportions of MyHCI and MyHCIIA fibers in offspring, while the proportion of MyHCIIX fibers was decreased (p<0.01). DNA methylation at the +530 cytosine-guanine dinucleotide (CpG) site of the myogenic factor 5 (MYF5) promoter in restricted fetuses was increased (p<0.05), but the methylation of the MYF5 gene at the +274,280 CpG site and of the myogenic differentiation (MYOD) gene at the +252 CpG site in restricted kids was reduced (p<0.05). mTOR protein signals were downregulated (p<0.05) in the restricted offspring.ConclusionMaternal undernutrition altered the muscle fiber type in offspring, but its relationship with methylation in the promoter regions of myogenic genes needs to be elucidated.
| S-EPMC9066034 | biostudies-literature
Project description:ObjectiveMaternal exposure during pregnancy is a strong determinant of offspring health outcomes. Such exposure induces changes in the offspring epigenome resulting in gene expression and functional changes. In this study, we investigated the effect of maternal Western hypercaloric diet (HCD) programming during the perinatal period on neuronal plasticity and cardiometabolic health in adult offspring.MethodsC57BL/6J dams were fed HCD for 1 month prior to mating with regular diet (RD) sires and kept on the same diet throughout pregnancy and lactation. At weaning, offspring were maintained on either HCD or RD for 3 months resulting in 4 treatment groups that underwent cardiometabolic assessments. DNA and RNA were extracted from the hypothalamus to perform whole genome methylation, mRNA, and miRNA sequencing followed by bioinformatic analyses.ResultsMaternal programming resulted in male-specific hypertension and hyperglycemia, with both males and females showing increased sympathetic tone to the vasculature. Surprisingly, programmed male offspring fed HCD in adulthood exhibited lower glucose levels, less insulin resistance, and leptin levels compared to non-programmed HCD-fed male mice. Hypothalamic genes involved in inflammation and type 2 diabetes were targeted by differentially expressed miRNA, while genes involved in glial and astrocytic differentiation were differentially methylated in programmed male offspring. These data were supported by our findings of astrogliosis, microgliosis and increased microglial activation in programmed males in the paraventricular nucleus (PVN). Programming induced a protective effect in male mice fed HCD in adulthood, resulting in lower protein levels of hypothalamic TGFβ2, NF-κB2, NF-κBp65, Ser-pIRS1, and GLP1R compared to non-programmed HCD-fed males. Although TGFβ2 was upregulated in male mice exposed to HCD pre- or post-natally, only blockade of the brain TGFβ receptor in RD-HCD mice improved glucose tolerance and a trend to weight loss.ConclusionsOur study shows that maternal HCD programs neuronal plasticity in the offspring and results in male-specific hypertension and hyperglycemia associated with hypothalamic inflammation in mechanisms and pathways distinct from post-natal HCD exposure. Together, our data unmask a compensatory role of HCD programming, likely via priming of metabolic pathways to handle excess nutrients in a more efficient way.
| S-EPMC10806294 | biostudies-literature
Project description:Aging is an inevitable and gradually progressive process affecting all organs and systems. The musculoskeletal system makes no exception, elderly exhibit an increased risk of sarcopenia (low muscle mass),dynapenia (declining muscle strength), and subsequent disability. Whereas in recent years the subject of skeletal muscle metabolic decline in the elderly has been gathering interest amongst researchers, as well as medical professionals, there are many challenges yet to be solved in order to counteract the effects of aging on muscle function efficiently. Noteworthy, it has been shown that aging individuals exhibit a decline in skeletal muscle metabolism, a phenomenon which may be linked to a number of predisposing (risk) factors such as telomere attrition, epigenetic changes, mitochondrial dysfunction, sedentary behavior (leading to body composition alterations), age-related low-grade systemic inflammation (inflammaging), hormonal imbalance, as well as a hypoproteic diet (unable to counterbalance the repercussions of the age-related increase in skeletal muscle catabolism). The present review aims to discuss the relationship between old age and muscle wasting in an effort to highlight the modifications in skeletal muscle metabolism associated with aging and physical activity.
| S-EPMC7014434 | biostudies-literature
Project description:Intrauterine or early postnatal high-fat diet (HFD) has substantial influences on adult offspring health; however, studies of HFD-induced maternal obesity on regulation of adult offspring bone formation are sparse. Here, we investigated the effects of HFD-induced maternal obesity on both fetal and adult offspring skeletal development. We found that HFD-induced maternal obesity significantly decreased fetal skeletal development, but enhanced fetal osteoblastic cell senescence signaling and significantly increased the expression of inflammatory factors of the senescence-associated secretory phenotype (SASP) in osteo-progenitors. It was found that p300/CBP activation led to H3K27 acetylation to increase the expression of senescence-related genes and PPARγ in embryonic mouse osteogenic calvarial cells from HFD obese dams. These results were recapitulated in human umbilical cord mesenchymal stem cells (UC MSCs) isolated from offspring of pregnant obese and lean mothers following delivery. Regardless of postnatal HFD challenge, adult offspring from HFD obese dams showed significantly suppressed bone formation. Such early involution of bone formation of adult offspring from HFD obese dams may at least in part due to histone acetylation, i.e., epigenetic regulation of genes involved in cell senescence signaling in pre-osteoblasts from prenatal development. These findings indicate fetal pre-osteoblastic cell senescence signaling is epigenetically regulated by maternal obesity to repress bone formation in adult offspring in rodents and suggest that at least some of these effects may also manifest in humans.
| S-EPMC6145139 | biostudies-literature
Project description:BackgroundMitochondria are of major importance in oocyte and early embryo, playing a key role in maintaining energy homeostasis. Epidemiological findings indicate that maternal undernutrition-induced mitochondrial dysfunction during pregnancy is associated with the development of metabolic disorders in offspring. Here, we investigated the effects of moderately decreased maternal energy intake during pregnancy on skeletal muscle mitochondrial biogenesis in fetal offspring with pig as a model.MethodsPregnant Meishan sows were allocated to a standard-energy (SE) intake group as recommended by the National Research Council (NRC; 2012) and a low-energy (LE) intake group. Fetal umbilical vein serum and longissimus muscle samples were collected for further analysis on day 90 of pregnancy.ResultsSow and fetal weights and the concentrations of serum growth hormone (GH) and glucose were reduced in LE group. Maternal LE diet decreased the messenger RNA (mRNA) expression of genes involved in mitochondrial biogenesis and function such as peroxisome proliferator-activated receptor gamma coactivator 1α (PPARGC1A), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), β subunit of mitochondrial H(+)-ATP synthase (ATB5B), sirtuin 1 (Sirt1), and citrate synthase (CS). The protein expression of PPARGC1A and Sirt1, intracellular NAD(+)-to-NADH ratio, and CS activity was reduced in LE group, and accordingly, mitochondrial DNA (mtDNA) content was decreased. Moreover, copper/zinc superoxide dismutase (CuZn-SOD) expression at both mRNA and protein levels and SOD and catalase (CAT) activities were reduced in LE group as well.ConclusionsThe observed decrease in muscle mitochondrial biogenesis and antioxidant defense capacity suggests that moderately decreased maternal energy intake during pregnancy impairs mitochondrial function in fetal pigs.
| S-EPMC4968452 | biostudies-literature