Maternal Obesity Increases Oxidative Stress in Placenta and It Is Associated With Intestinal Microbiota.
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ABSTRACT:
SUBMITTER: Hu C
PROVIDER: S-EPMC8420882 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Maternal obesity is associated with placental oxidative stress. However, the mechanism underlying this association remains poorly understood. In the present study, a gilt obesity model was developed by exposure to different energy diets and used to investigate the role of NADPH oxidase 2 (Nox2) in the placenta. Specifically, 99 gilts (Guangdong Small-ear Spotted pig) at day 60 of gestation were randomly assigned to one of the following three treatments: low-energy group (L, DE = 11.50 MJ/kg), medium-energy group (M, DE = 12.41 MJ/kg), and high-energy group (H, DE = 13.42 MJ/kg), with 11 replicate pens per treatment and 3 gilts per pen. At the start of the study, maternal body weight and backfat thickness were not significantly different in the three treatments. After the study, data indicated that the H group had higher body weight and backfat thickness gain for gilts during gestation and lower piglet birth weight compared with the other two groups. Additionally, the H group showed glucolipid metabolic disorders and increased triglyceride and nonesterified fatty acid contents in the placenta of gilts. Compared with the L group, the H group exhibited lower mitochondrial biogenesis and increased oxidative damage in the placenta. Importantly, increased mRNA expression and protein abundance of Nox2 were observed for the first time in H group placentae. Furthermore, compared with the L group, the H group showed a decrease in the density of placental vessels and the protein levels of vascular endothelial cadherin (VE-cadherin), vascular endothelial growth factor A (VEGF-A), and phosphorylation of vascular endothelial growth factor receptor 2 (p-VEGFR2) as well as the immunostaining intensity of platelet endothelial cell adhesion molecule-1 (CD31). Our findings suggest that maternal high-energy diet-induced obesity increases placental oxidative stress and decreases placental angiogenesis possibly through the upregulation of Nox2.
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Project description:Maternal obese environment has been reported to induce oxidative stress and meiotic defects in oocytes, however the underlying molecular mechanism remains unclear. Here, using mice fed a high fat diet (HFD) as an obesity model, we first detected enhanced reactive oxygen species (ROS) content and reduced Sirt3 expression in HFD oocytes. We further observed that specific depletion of Sirt3 in control oocytes elevates ROS levels while Sirt3 overexpression attenuates ROS production in HFD oocytes, with significant suppression of spindle disorganization and chromosome misalignment phenotypes that have been reported in the obesity model. Candidate screening revealed that the acetylation status of lysine 68 on superoxide dismutase (SOD2K68) is dependent on Sirt3 deacetylase activity in oocytes, and acetylation-mimetic mutant SOD2K68Q results in almost threefold increase in intracellular ROS. Moreover, we found that acetylation levels of SOD2K68 are increased by ~80% in HFD oocytes and importantly, that the non-acetylatable-mimetic mutant SOD2K68R is capable of partially rescuing their deficient phenotypes. Together, our data identify Sirt3 as an important player in modulating ROS homeostasis during oocyte development, and indicate that Sirt3-dependent deacetylation of SOD2 plays a protective role against oxidative stress and meiotic defects in oocytes under maternal obese conditions.
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Project description:BackgroundOxidative stress in placenta is associated with the occurrence of adverse pregnancy outcomes in sow, but there are few satisfactory treatment strategies for these conditions. This study investigated the potential of cysteamine (CS) as an antioxidant protectant for regulating the reproductive performance, redox status, and placental angiogenesis of sows.MethodsThe placental oxidative stress status and vascular density of piglets with different birth weights: < 1.0 kg (low birth weight, LBW) and 1.4-1.6 kg (normal birth weight, NBW) were evaluated, followed by allotting 84 sows to four treatments (n = 21) and feeding them with a basal diet supplemented with 0, 100, 300, or 500 mg/kg of CS from d 85 of gestation to d 21 of lactation, respectively. Placenta, serum, and colostrum samples of sows or piglets were collected, and the characteristics of sows and piglets were recorded. Furthermore, the in vivo results were validated using porcine vascular endothelial cells (PVECs).ResultsCompared with the NBW placentae, the LBW placentae showed increased oxidative damage and were vulnerable to angiogenesis impairment. Particularly, H2O2-induced oxidative stress prompted intracellular reactive oxygen species generation and inhibited the tube formation and migration of PVECs as well as the expression of vascular endothelial growth factor-A (VEGF-A) in vitro. However, dietary CS supplementation can alleviate oxidative stress and improve the reproductive performance of sows. Specifically, compared with the control group, dietary 100 mg/kg CS could (1) decrease the stillbirth and invalid rates, and increase both the piglet birth weight in the low yield sows and the placental efficiency; (2) increase glutathione and reduce malondialdehyde in both the serum and the colostrum of sows; (3) increase the levels of total antioxidant capacity and glutathione in LBW placentae; (4) increase the vascular density, the mRNA level of VEGF-A, and the immune-staining intensity of platelet endothelial cell adhesion molecule-1 in the LBW placentae. Furthermore, the in vitro experiment indicated that CS pre-treatment could significantly reverse the NADPH oxidase 2-ROS-mediated inactivation of signal transducer and activator of transcription-3 (Stat3) signaling pathway induced by H2O2 inhibition of the proliferation, tube formation, and migration of PVECs. Meanwhile, inhibition of Stat3 significantly decreased the cell viability, tube formation and the VEGF-A protein level in CS pretreated with H2O2-cultured PVECs.ConclusionsThe results indicated that oxidative stress and impaired angiogenesis might contribute to the occurrence of LBW piglets during pregnancy, but CS supplementation at 100 mg/kg during late gestation and lactation of sows could alleviate oxidative stress and enhance angiogenesis in placenta, thereby increasing birth weight in low yield sows and reducing stillbirth rate. The in vitro data showed that the underlying mechanism for the positive effects of CS might be related to the activation of Stat3 in PVECs.
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Project description:Overweight and obesity have become a world-health public problem, mainly for developing countries. Both health conditions have a higher prevalence among women of childbearing age. Physiopathology, overweight and obesity are characterized by a chronic oxidative stress status, which has deleterious effects on mothers and children. Hence, we determine whether the qualities of diet during pregnancy and maternal pregestational body mass index (BMI) are associated with increased oxidative stress markers in mothers and newborns. Two hundred forty-two (242) mother-newborn pairs were classified according to their pregestational BMI. Information on food intake was collected using a food frequency questionnaire in the third trimester of pregnancy. Levels of Malondialdehyde (MDA) and Nitric Oxide (NO) were measured in plasma from mothers at the end of the third trimester of pregnancy and from cord blood at birth. MDA and NO levels in mother-newborn pairs with maternal pregestational overweight or obesity were higher than in mother-newborn pairs with pregestational normal weight. For women (and newborns) who had a higher intake of fruit and vegetables, the levels of NO and MDA were lower. Lastly, women with pregestational obesity had lower fruit and vegetable intake during pregnancy and higher levels of oxidative stress and in their newborns.
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Project description:Auricularia delicate (ADe), an edible fungus belonging to the family Auriculariaceae and order Auriculariales, possesses antimicrobial, hepatoprotective, and antioxidant effects. In this study, after systematic analysis of its composition, ADe was administered to high-fat-diet (HFD)-fed mice to investigate its anti-obesity effect. ADe significantly controlled body weight; alleviated hepatic steatosis and adipocyte hypertrophy; reduced aspartate aminotransferase, total cholesterol, insulin, and resistin; and increased adiponectin levels in HFD-fed mice serum. Based on intestinal microbiota and lipidomics analysis, ADe treatment regulated the composition and abundance of 49 intestinal microorganisms and influenced the abundance of 8 lipid species compared with HFD-fed mice. Based on a correlation analysis of the intestinal microbiota and lipids, Coprococcus showed significant negative associations with ceramide (d18:0 20:0+O), phosphatidylserine (39:4), sphingomyelin (d38:4), and zymosterol (20:2). Moreover, ADe treatment decreased the levels of ROS and MDA and increased the levels of Nrf2, HO-1, and three antioxidant enzymes in HFD-fed mice livers. Collectively, the anti-obesity effect of ADe involves the regulation of oxidative stress and is mediated by the intestinal microbiota. Hence, this study provides a reference for the application of ADe as a candidate food for obesity.
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Project description:Increased Lipoprotein associated phospholipase A2 (LpPLA2) has been associated with inflammatory pathologies, including Type 2 Diabetes. Studies on LpPLA2 and Gestational Diabetes Mellitus (GDM) are rare, and have focused mostly on maternal outcome. In the present study, we investigated whether LpPLA2 activity on foetal lipoproteins is altered by maternal GDM and/or obesity (a major risk factor for GDM), thereby contributing to changes in lipoprotein functionality. We identified HDL as the major carrier of LpPLA2 activity in the foetus, which is in contrast to adults. We observed marked expression of LpPLA2 in placental macrophages (Hofbauer cells; HBCs) and found that LpPLA2 activity in these cells was increased by insulin, leptin, and pro-inflammatory cytokines. These regulators were also increased in plasma of children born from GDM pregnancies. Our results suggest that insulin, leptin, and pro-inflammatory cytokines are positive regulators of LpPLA2 activity in the foeto-placental unit. Of particular interest, functional assays using a specific LpPLA2 inhibitor suggest that high-density lipoprotein (HDL)-associated LpPLA2 exerts anti-oxidative, athero-protective functions on placental endothelium and foetus. Our results therefore raise the possibility that foetal HDL-associated LpPLA2 might act as an anti-inflammatory enzyme improving vascular barrier function.
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Project description:Obesity represents a major risk factor for a plethora of severe diseases, including diabetes, cardiovascular disease, non-alcoholic fatty liver disease, and cancer. It is often accompanied by an increased risk of mortality and, in the case of non-fatal health problems, the quality of life is impaired because of associated conditions, including sleep apnea, respiratory problems, osteoarthritis, and infertility. Recent evidence suggests that oxidative stress may be the mechanistic link between obesity and related complications. In obese patients, antioxidant defenses are lower than normal weight counterparts and their levels inversely correlate with central adiposity; obesity is also characterized by enhanced levels of reactive oxygen or nitrogen species. Inadequacy of antioxidant defenses probably relies on different factors: obese individuals may have a lower intake of antioxidant- and phytochemical-rich foods, such as fruits, vegetables, and legumes; otherwise, consumption of antioxidant nutrients is normal, but obese individuals may have an increased utilization of these molecules, likewise to that reported in diabetic patients and smokers. Also inadequate physical activity may account for a decreased antioxidant state. In this review, we describe current concepts in the meaning of obesity as a state of chronic oxidative stress and the potential interventions to improve redox balance.
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Project description:We aimed to investigate the role of capsaicin (CAP) in modulating lipopolysaccharide (LPS)-induced hepatic and intestinal inflammation, oxidative stress, and its colonic microflora in mice. Thirty healthy male Kunming mice with similar body weights were randomly assigned to three groups: the control group (CON), the LPS group, and the CAP group, with ten mice in each group. The CON and the LPS groups received a daily dose of normal saline, respectively, while the CAP group received an equivalent dose of CAP. On the 28th day of the experiment, the LPS and the CAP groups were intraperitoneally injected with LPS, while the CON group was injected with an equal volume of normal saline. The results lead to the following conclusions. Compared to the LPS group, CAP improved the loss of hepatic lobular structure and significantly increased the duodenal villus length and ratio of villus length to crypt depth. CAP increased hepatic and colon interleukin-10 (IL-10) and decreased IL-6, IL-1β, and tumor necrosis factor (TNF-α) levels. CAP also increased hepatic catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) expression, and decreased malondialdehyde (MDA) levels. CAP significantly increased the relative abundances of Mucispirillum, Helicobacter, Prevotellaceae-UCG-001, Colidextribacter, unclassified-f-Oscillospiraceae, and Odoribacter, some of which were closely related to hepatic and colonic immune and oxidative markers. CAP also decreased the overall content of short-chain fatty acids, except for propionic acid. Overall, CAP can regulate the colon microbiota and exert anti-inflammatory and antioxidant effects. Whether CAP exerts its anti-inflammatory and antioxidant effects by modulating the colonic microflora, mainly Mucispirillum spp. and Helicobacter spp., requires further investigation.
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Project description:BackgroundObesity before pregnancy is associated with impaired metabolic status of the mother and the offspring later in life. These adverse effects have been attributed to epigenetic changes in utero, but little is known about the role of placental metabolism and its contribution to fetal development.ObjectivesWe examined the impact of maternal pre-pregnancy obesity on the expression of genes involved in placental lipid metabolism in lean and obese women.Subjects/methodsSeventy-three lean and obese women with healthy pregnancy were recruited at term elective cesarean delivery. Metabolic parameters were measured on maternal venous blood samples. Expression of 88 genes involved in lipid metabolism was measured in whole placenta tissue. Proteins of genes differently expressed in response to maternal obesity were quantified, correlated with maternal parameters and immunolocalized in placenta sections. Isolated primary trophoblasts were used for in vitro assays.ResultsTriglyceride (TG) content was increased in placental tissue of obese (1.10, CI 1.04-1.24 mg g-1, P<0.05) vs lean (0.84, CI 0.72-1.02 mg g-1) women. Among target genes examined, six showed positive correlation (P<0.05) with maternal pre-pregnancy BMI, namely ATGL (PNPLA2), FATP1 (SLC27A1), FATP3 (SLC27A3), PLIN2, PPARG and CGI-58 (ABHD5). CGI-58 protein abundance was twofold higher (P<0.001) in placentas of obese vs lean women. CGI-58 protein levels correlated positively with maternal insulin levels and pre-pregnancy body mass index (R=0.63, P<0.001 and R=0.64, P<0.001, respectively). CGI-58 and PLIN2 were primarily located in the syncytiotrophoblast and, were upregulated (1.38- and 500-fold, respectively) upon oleic acid and insulin treatment of cultured trophoblast cells.ConclusionPre-gravid obesity significantly modifies the expression of placental genes related to transport and storage of neutral lipids. We propose that the upregulation of CGI-58, a master regulator of TG hydrolysis, contributes to the turnover of intracellular lipids in placenta of obese women, and is tightly regulated by metabolic factors of the mother.
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Project description:In the present study, we investigated the influence of diquat-induced oxidative stress on intestinal barrier, mitochondrial function, and the level of mitophagy in piglets. Twelve male Duroc × Landrace × Yorkshire 35-d-old pigs (weaned at 21 d of age), with an average body of 9.6 kg, were allotted to two treatments of six piglets each including the challenged group and the control group. The challenged pigs were injected with 100 mg/kg bodyweight diquat and control pigs injected with 0.9% (w/v) NaCl solution. The results showed that diquat injection decreased ADFI and ADG. Diquat decreased (P < 0.05) the activities of superoxide dismutase and glutathione peroxidase and increased (P < 0.05) the malondialdehyde concentrations. The lower (P < 0.05) transepithelial electrical resistance and higher (P < 0.05) paracellular permeability of fluorescein isothiocyanatedextran 4 kDa were found in diquat challenged piglets. Meanwhile, diquat decreased (P < 0.05) the protein abundance of claudin-1, occluding, and zonula occludens-1 in jejunum compared with the control group. Diquat-induced mitochondrial dysfunction, as demonstrated by increased (P < 0.05) reactive oxygen species production and decreased (P < 0.05) membrane potential of intestinal mitochondria. Diquat-injected pigs revealed a decrease (P < 0.05) of mRNA abundance of genes related to mitochondrial biogenesis and functions, PPARg coactivator-1α, mammalian-silencing information regulator-1, nuclear respiratory factor-1, mt transcription factor A, mt single-strand DNA-binding protein, mt polymerase r, glucokinase, citrate synthase, ATP synthase, and cytochrome coxidase subunit I and V in the jejunum. Diquat induced an increase (P < 0.05) in expression of mitophagy-related proteins, phosphatase and tensin homologue deleted on chromosome 10-induced putative kinase, and Parkin in the intestinal mitochondria, as well as an enhancement of the ratio of light chain 3-II (LC3-II) to LC3-I content in the jejunal mucosa. These results suggest that oxidative stress disrupted the intestinal barrier, caused mitochondrial dysfunction, and triggered mitophagy.
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