Maternal exercise via exerkine apelin enhances brown adipogenesis and prevents metabolic dysfunction in offspring mice.
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ABSTRACT:
SUBMITTER: Son JS
PROVIDER: S-EPMC7164955 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Although maternal exercise (ME) becomes increasingly uncommon, the effects of ME on offspring muscle metabolic health remain largely undefined. Maternal mice are subject to daily exercise during pregnancy, which enhances mitochondrial biogenesis during fetal muscle development; this is correlated with higher mitochondrial content and oxidative muscle fibers in offspring muscle and improved endurance capacity. Apelin, an exerkine, is elevated due to ME, and maternal apelin administration mirrors the effect of ME on mitochondrial biogenesis in fetal muscle. Importantly, both ME and apelin induce DNA demethylation of the peroxisome proliferator-activated receptor γ coactivator-1α (Ppargc1a) promoter and enhance its expression and mitochondrial biogenesis in fetal muscle. Such changes in DNA methylation were maintained in offspring, with ME offspring muscle expressing higher levels of PGC-1α1/4 isoforms, explaining improved muscle function. In summary, ME enhances DNA demethylation of the Ppargc1a promoter in fetal muscle, which has positive programming effects on the exercise endurance capacity and protects offspring muscle against metabolic dysfunction.
| S-EPMC8137280 | biostudies-literature
Project description:Low intensity exercise during pregnancy and lactation may create a protective effect against the development of obesity in offspring exposed to overnutrition in early life. To test these hypotheses, pregnant rats were randomly assigned into 2 groups: Sedentary and Exercised, low intensity, on a rodent treadmill at 30% VO2Max /30-minute/session/3x/week throughout pregnancy and the lactation. Male offspring were raised in small litters (SL, 3 pups/dam) and normal litters (NL, 9 pups/dam) as models of early overnutrition and normal feed, respectively. Exercised mothers showed low mesenteric fat pad stores and fasting glucose and improved glucose-insulin tolerance, VO2max during lactation and sympathetic activity. Moreover, the breast milk contained elevated levels of insulin. In addition, SL of sedentary mothers presented metabolic dysfunction and glucose and insulin intolerance and were hyperglycemic and hyperinsulinemic in adulthood. SL of exercised mothers showed lower fat tissue accretion and improvements in glucose tolerance, insulin sensitivity, insulinemia and glycemia. The results suggest that maternal exercise during the perinatal period can have a possible reprogramming effect to prevent metabolic dysfunction in adult rat offspring exposed to early overnutrition, which may be associated with the improvement in maternal health caused by exercise.
| S-EPMC5550501 | biostudies-other
Project description:Brown adipose tissue (BAT) is a central thermogenic organ that enhances energy expenditure and cardiometabolic health. However, regulators that specifically increase the number of thermogenic adipocytes are still an unmet need. Here, we show that the cAMP-binding protein EPAC1 is a central regulator of adaptive BAT growth. In vivo, selective pharmacological activation of EPAC1 increases BAT mass and browning of white fat, leading to higher energy expenditure and reduced diet-induced obesity. Mechanistically, EPAC1 coordinates a network of regulators for proliferation specifically in thermogenic adipocytes, but not in white adipocytes. We pinpoint the effects of EPAC1 to PDGFRα-positive preadipocytes, and the loss of EPAC1 in these cells impedes BAT growth and worsens diet-induced obesity. Importantly, EPAC1 activation enhances the proliferation and differentiation of human brown adipocytes and human brown fat organoids. Notably, a coding variant of RAPGEF3 (encoding EPAC1) that is positively correlated with body mass index abolishes noradrenaline-induced proliferation of brown adipocytes. Thus, EPAC1 might be an attractive target to enhance thermogenic adipocyte number and energy expenditure to combat metabolic diseases.
| S-EPMC10791580 | biostudies-literature
Project description:Poor maternal diet can lead to metabolic disease in offspring, whereas maternal exercise may have beneficial effects on offspring health. In this study, we determined ifmaternal exercise could reverse the detrimental effects of maternal high-fat feeding on offspring metabolism of female mice. C57BL/6 female mice were fed a chow (21%) or high-fat (60%) diet and further divided by housing in static cages or cages with running wheels for 2 weeks prior to breeding and throughout gestation. Females were bred with chow-fed sedentary C57BL/6 males. High fat-fed sedentary dams produced female offspring with impaired glucose tolerance compared with offspring of chow-fed dams throughout their first year of life, an effect not present in the offspring from high fat-fed dams that had trained. Offspring from high fat-fed trained dams had normalized glucose tolerance, decreased fasting insulin, and decreased adiposity. Liver metabolic function, measured by hepatic glucose production in isolated hepatocytes, hyperinsulinemic-euglycemic clamps, liver triglyceride content, and liver enzyme expression, was enhanced in offspring from trained dams. In conclusion, maternal exercise negates the detrimental effects of a maternal high-fat diet on glucose tolerance and hepatocyte glucose metabolism in female offspring. The ability of maternal exercise to improve the metabolic health of female offspring is important, as this intervention could combat the transmission of obesity and diabetes to subsequent generations.
| S-EPMC5521858 | biostudies-other
Project description:Pulmonary fibrosis is a progressive disease characterized by epithelial cell damage, fibroblast proliferation, excessive extracellular matrix (ECM) deposition, and lung tissue scarring. Melatonin, a hormone produced by the pineal gland, plays an important role in multiple physiological and pathological responses in organisms. However, the function of melatonin in the development of bleomycin-induced pulmonary injury is poorly understood. In the present study, we found that melatonin significantly decreased mortality and restored the function of the alveolar epithelium in bleomycin-treated mice. However, pulmonary function mainly depends on type II alveolar epithelial cells (AECIIs) and is linked to mitochondrial integrity. We also found that melatonin reduced the production of reactive oxygen species (ROS) and prevented apoptosis and senescence in AECIIs. Luzindole, a nonselective melatonin receptor antagonist, blocked the protective action of melatonin. Interestingly, we found that the expression of apelin 13 was significantly downregulated in vitro and in vivo and that this downregulation was reversed by melatonin. Furthermore, ML221, an apelin inhibitor, disrupted the beneficial effects of melatonin on alveolar epithelial cells. Taken together, these results suggest that melatonin alleviates lung injury through regulating apelin 13 to improve mitochondrial dysfunction in the process of bleomycin-induced pulmonary injury.
| S-EPMC6802616 | biostudies-literature
Project description:Regular exercise during pregnancy can prevent offspring from several diseases, such as cardiovascular diseases, obesity, and type II diabetes during adulthood. However, little information is available about whether maternal exercises during pregnancy protect the offspring from infectious diseases, such as sepsis and multiple organ dysfunction syndrome (MODS). This study aimed to investigate whether maternal exercise training protects the offspring from endotoxin-induced septic shock in mice. Female C57BL/6 mice performed voluntary wheel exercises during pregnancy. All dams and offspring were fed normal chow with sedentary activity during lactation and after weaning. At 10-week-old, mice were intraperitoneally injected a lethal (30?mg/kg) or nonlethal (15?mg/kg) dose of lipopolysaccharide (LPS), following which the survival of mice that were administered a lethal dose was monitored for 60?h. Plasma, lung, and liver samples were collected 18?h after the injection to evaluate the cytokine concentration or mRNA expression from those administered a nonlethal dose. Although maternal exercise training could not prevent lethality during an LPS-induced septic shock, it significantly inhibited the LPS-induced loss of body weight in female offspring. Regular maternal exercise significantly inhibited the mRNA expression of the LPS-induced inflammatory cytokines, such as interleukin-1? (IL-1?) and interferon-? (IFN-?), in the plasma and liver. Thus, maternal exercise inhibited the LPS-induced inflammatory response in female offspring, suggesting that regular exercise during pregnancy could be a potential candidate of the onset of sepsis and MODS in offspring.
| S-EPMC6008276 | biostudies-other
Project description:BackgroundSarcolipin and uncoupling protein 3 (UCP3) mediate muscle-based non-shivering thermogenesis (NST) to improve metabolic homeostasis. The impacts of maternal obesity (MO) and maternal exercise (ME) on NST in offspring muscle remain unexamined.MethodsFemale mice were fed with a control diet or high fat diet to induce obesity. Then, obese mice were further separated into two groups: obesity only (OB) and OB plus daily exercise (OB/Ex). Fetal muscle was collected at embryonic day 18.5 and offspring mice at 3-month-old. Apelin administration during pregnancy and apelin receptor (APJ) knockout mouse were further used for investigating the mediatory role of APJ on muscle-based thermogenesis. To explore the direct effects of exercise on AMP-activated protein kinase (AMPK) downstream targets, AMPK knockout mouse was used.FindingsMO inhibited while ME activated AMPK and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in fetal muscle. AMPK activation increased sarcolipin expression, which inhibited the uptake of calcium ions into sarcoplasmic reticulum, thereby activating CaMKK2. Consistently, the expression of UCP3 and sarcolipin was suppressed due to MO but activated in ME fetal muscle. Importantly, changes of UCP3 and sarcolipin maintained in offspring muscle, showing the transgenerational effects. Furthermore, apelin administration during pregnancy mimicked the effects of ME on AMPK and CaMKK2 activation, and UCP3 and sarcolipin expression, underscoring the mediatory roles of apelin-AMPK signaling in improving fetal muscle development.InterpretationME, via activation of apelin signaling-AMPK axis, enhances NST gene expression in fetal and offspring muscle impaired due to MO, which intergenerationally protects offspring from diet-induced obesity and metabolic disorders.FundingThis work was supported by National Institutes of Health Grant R01-HD067449.
| S-EPMC8790600 | biostudies-literature
Project description:A variety of environmental factors contribute significantly to age-related cognitive decline and memory impairment in Alzheimer's Disease (AD) and other neurodegenerative diseases. Nutrition can alter epigenetics, improving health outcomes, which can be transmitted across generations; this process is called epigenetic inheritance. We investigate the beneficial effects of maternal resveratrol supplementation in the direct exposed F1 generation and the transgenerational F2 generation. The offspring was generated from females Senescence Accelerated Mouse-Prone (SAMP8) fed a resveratrol-enriched diet for two months prior to mating. Object novel recognition and Morris Water Maze (MWM) demonstrated improvements in cognition in the 6-month-old F1 and F2 generations from resveratrol fed mothers. A significant increase in global DNA methylation with a decrease in hydroxymethylation in F1 and F2 were found. Accordingly, Dnmt3a/b and Tet2 gene expression changed. Methylation levels of Nrf2 and NF-kβ genes promoters raised in offspring, inducing changes in target genes expression, as well as hydrogen peroxide levels. Offspring that resulted from a resveratrol fed mother showed increase AMPKα activation, mTOR inhibition, and an increase in Pgc-1α gene expression and Beclin-1 protein levels. Endoplasmic reticulum stress sensors were found changed both in F1 and F2 generations. Overall, our results demonstrated that maternal resveratrol supplementation could prevent cognitive impairment in the SAMP8 mice offspring through epigenetic changes and cell signaling pathways.
| S-EPMC6429303 | biostudies-literature
Project description:The intrauterine environment can modulate the course of development and confer an enduring effect on offspring health. The effects of maternal diet to impair offspring metabolic health are well established, but the effects of maternal exercise on offspring metabolic health have been less defined. Because physical exercise is a treatment for obesity and type 2 diabetes (T2D), maternal exercise is an appealing intervention to positively influence the intrauterine environment and improve the metabolic health of offspring. Recent research has provided insights into the effects of maternal exercise on the metabolic health of adult offspring, which is the focus of this review.
| S-EPMC5826804 | biostudies-literature
Project description:The intrauterine environment during pregnancy is a critical factor in the development of diabetes and obesity in offspring. To determine the effects of maternal exercise during pregnancy on the metabolic health of offspring, 6-week-old C57BL/6 virgin female mice were fed a chow (21%) or high-fat (60%) diet and divided into four subgroups: trained (housed with running wheels for 2 weeks preconception and during gestation), prepregnancy trained (housed with running wheels for 2 weeks preconception), gestation trained (housed with running wheels during gestation), or sedentary (static cages). Male offspring were chow fed, sedentary, and studied at 8, 12, 24, 36, and 52 weeks of age. Offspring from chow-fed dams that trained both before and during gestation had improved glucose tolerance beginning at 8 weeks of age and continuing throughout the 1st year of life, and at 52 weeks of age had significantly lower serum insulin concentrations and percent body fat compared with all other groups. High-fat feeding of sedentary dams resulted in impaired glucose tolerance, increased serum insulin concentrations, and increased percent body fat in offspring. Remarkably, maternal exercise before and during gestation ameliorated the detrimental effect of a maternal high-fat diet on the metabolic profile of offspring. Exercise before and during pregnancy may be a critical component for combating the increasing rates of diabetes and obesity.
| S-EPMC4303966 | biostudies-literature