Resveratrol attenuates mitochondrial dysfunction in the liver of intrauterine growth retarded suckling piglets by improving mitochondrial biogenesis and redox status

Abstract The present study used intrauterine growth restriction (IUGR) piglets as an animal model to determine the effect of Bacillus subtilis on intestinal integrity, antioxidant capacity, and microbiota in the jejunum of suckling piglets. In total, 8 normal birth weight (NBW) newborn piglets (1.62 ± 0.10 kg) and 16 newborn IUGR piglets (0.90 ± 0.08 kg) were selected and assigned to 3 groups. Piglets were orally gavaged with 10 mL sterile saline (NBW and IUGR groups), IUGR piglets were orally gavaged with 10 mL/d bacterial fluid (Bacillus subtilis diluted in sterile saline, gavage in the dose of 2 × 109 colony-forming units per kg of body weight) (IBS group) (n = 8). IUGR induced jejunal barrier dysfunction and redox status imbalance of piglets, and changed the abundances of bacteria in the jejunum. Treatment with Bacillus subtilis increased (P < 0.05) the ratio of villus height to crypt depth (VH/CD) in the jejunum, decreased (P < 0.05) the plasma diamine oxidase (DAO) activity, and enhanced (P < 0.05) the gene expressions of zonula occludens-1 (ZO-1), Occludin and Claudin-1 in the jejunum of IUGR piglets. Treatment with Bacillus subtilis decreased (P < 0.05) the concentration of protein carbonyl (PC), and increased (P < 0.05) the activities of catalase (CAT) and total superoxide dismutase (T-SOD) in the jejunum of IUGR piglets. Treatment with Bacillus subtilis also increased (P < 0.05) gene expressions of superoxide dismutase 1 (SOD1), CAT, and nuclear factor erythroid 2-related factor (Nrf2), as well as the protein expressions of heme oxygenase-1 (HO-1), SOD1, and Nrf2 in the jejunum of IUGR piglets. Treatment with Bacillus subtilis also improved the abundances and the community structure of bacteria in the jejunum of IUGR piglets. These results suggested that IUGR damaged the jejunal barrier function and antioxidant capacity of suckling piglets, altered the abundances of bacteria in the jejunum. Treatment with Bacillus subtilis improved the intestinal integrity and antioxidant capacity, while also improved the abundances and structure of bacteria in the jejunum of suckling piglets.

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Effects of dietary leucine supplementation on the hepatic mitochondrial biogenesis and energy metabolism in normal birth weight and intrauterine growth-retarded weanling piglets

Nutrition Research and Practice ◽

10.4162/nrp.2017.11.2.121 ◽

2017 ◽

Vol 11 (2) ◽

pp. 121 ◽

Cited By ~ 8

Author(s):

Weipeng Su ◽

Wen Xu ◽

Hao Zhang ◽

Zhixiong Ying ◽

Le Zhou ◽

...

Keyword(s):

Birth Weight ◽

Energy Metabolism ◽

Mitochondrial Biogenesis ◽

Normal Birth Weight ◽

Leucine Supplementation ◽

Intrauterine Growth ◽

Normal Birth ◽

Weanling Piglets

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DNA Methylation of PGC-1α Is Associated With Elevated mtDNA Copy Number and Altered Urinary Metabolites in Autism Spectrum Disorder

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.696428 ◽

2021 ◽

Vol 9 ◽

Author(s):

Sophia Bam ◽

Erin Buchanan ◽

Caitlyn Mahony ◽

Colleen O’Ryan

Keyword(s):

Autism Spectrum Disorder ◽

Dna Methylation ◽

Mitochondrial Dysfunction ◽

Mitochondrial Biogenesis ◽

Mitochondrial Function ◽

Copy Number ◽

Autism Spectrum ◽

Differential Methylation ◽

Mtdna Copy Number ◽

Key Genes

Autism spectrum disorder (ASD) is a complex disorder that is underpinned by numerous dysregulated biological pathways, including pathways that affect mitochondrial function. Epigenetic mechanisms contribute to this dysregulation and DNA methylation is an important factor in the etiology of ASD. We measured DNA methylation of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), as well as five genes involved in regulating mitochondrial homeostasis to examine mitochondrial dysfunction in an ASD cohort of South African children. Using targeted Next Generation bisulfite sequencing, we found differential methylation (p < 0.05) at six key genes converging on mitochondrial biogenesis, fission and fusion in ASD, namely PGC-1α, STOML2, MFN2, FIS1, OPA1, and GABPA. PGC-1α, the transcriptional regulator of biogenesis, was significantly hypermethylated at eight CpG sites in the gene promoter, one of which contained a putative binding site for CAMP response binding element 1 (CREB1) (p = 1 × 10–6). Mitochondrial DNA (mtDNA) copy number, a marker of mitochondrial function, was elevated (p = 0.002) in ASD compared to controls and correlated significantly with DNA methylation at the PGC-1α promoter and there was a positive correlation between methylation at PGC-1α CpG#1 and mtDNA copy number (Spearman’s r = 0.2, n = 49, p = 0.04) in ASD. Furthermore, DNA methylation at PGC-1α CpG#1 and mtDNA copy number correlated significantly (p < 0.05) with levels of urinary organic acids associated with mitochondrial dysfunction, oxidative stress, and neuroendocrinology. Our data show differential methylation in ASD at six key genes converging on PGC-1α-dependent regulation of mitochondrial biogenesis and function. We demonstrate that methylation at the PGC-1α promoter is associated with elevated mtDNA copy number and metabolomic evidence of mitochondrial dysfunction in ASD. This highlights an unexplored role for DNA methylation in regulating specific pathways involved in mitochondrial biogenesis, fission and fusion contributing to mitochondrial dysfunction in ASD.

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Dexmedetomidine Attenuates Lung Ischemia-reperfusion Injury in Rats by Reducing Mitochondrial Dysfunction

10.21203/rs.3.rs-120188/v1 ◽

2020 ◽

Author(s):

Yan Zhang ◽

Yao Lu ◽

Kai Wang ◽

Mei-yan Zhou ◽

Cong-you Wu ◽

...

Keyword(s):

Mitochondrial Dysfunction ◽

Reperfusion Injury ◽

Mitochondrial Biogenesis ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Weight Ratio ◽

Oxygenation Index ◽

Lung Damage ◽

Peroxisome Proliferator ◽

Sprague Dawley

Abstract Background: Lung ischemia-reperfusion injury (LIRI) is a significant clinical problem occurring after lung transplantation. LIRI is mediated by the overproduction of reactive oxygen species (ROS) and inflammatory activation. Previous studies have confirmed that dexmedetomidine (DEX) exerts a protective effect on LIRI, which potentially causes severe mitochondrial dysfunction. However, the specific mechanisms remain unclear. Our study was to explore whether dexmedetomidine exerts a beneficial effect on LIRI by reducing mitochondrial dysfunction. Methods: Two different models were used in our study. For the in vivo experiment, thirty-two male Sprague-Dawley rats were randomly divided into Sham, ischemia-reperfusion (I/R), DEX+I/R and DEX+yohimbine+I/R (DY+I/R) groups. Similarly, pulmonary vascular endothelial cells (PVECs) from SD rats were divided into Control, oxygen glucose deprivation (OGD), D+OGD and DY+OGD groups.Results: In our experiment, we confirmed severe lung damage after LIRI that was characterized by significantly pulmonary histopathology injury, a decrease in the oxygenation index (PaO2/FiO2) and an increase in the wet-to-dry weight ratio, while DEX treatment mitigated this damage. In addition, the DEX pretreatment significantly attenuated I/R-induced oxidative stress by decreasing the level of ROS in the mitochondria in vitro. Moreover, the DEX treatment enhanced mitochondrial biogenesis and autophagy by increasing the expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), mitochondrial transcription factor A (Tfam), PTEN-induced putative kinase 1 (PINK1), Parkin and dynamin 1-like protein 1 (Drp1). Conclusions: These data suggest that DEX may alleviate LIRI by reducing mitochondrial dysfunction through the induction of mitochondrial biogenesis and autophagy.

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Dietary dimethylglycine sodium salt supplementation improves growth performance, redox status, and skeletal muscle function of intrauterine growth restriction weaned piglets

Journal of Animal Science ◽

10.1093/jas/skab186 ◽

2021 ◽

Author(s):

Kaiwen Bai ◽

Luyi Jiang ◽

Qiming Li ◽

Jingfei Zhang ◽

Lili Zhang ◽

...

Keyword(s):

Growth Performance ◽

Mitochondrial Function ◽

Chain Complex ◽

Basal Diet ◽

Mitochondrial Respiratory Chain ◽

Redox Status ◽

Weaned Piglets ◽

Complex Activity ◽

Mitochondrial Respiratory Chain Complex ◽

Intrauterine Growth

Abstract Few studies have focused on the role of dimethylglycine sodium salt (DMG-Na) in protecting the redox status of skeletal muscle, although it is reported to be beneficial in animal husbandry. This study investigated the beneficial effects of DMG-Na on the growth performance, longissimus dorsi muscle (LM) redox status, and mitochondrial function in weaning piglets that were intrauterine growth restricted (IUGR). Ten normal birth weight (NBW) newborn piglets (1.53 ± 0.04 kg) and 20 IUGR newborn piglets (0.76 ± 0.06 kg) from ten sows were obtained. All piglets were weaned at 21 days of age and allocated to three groups with ten replicates per group: NBW-weaned piglets fed a common basal diet (N); IUGR weaned piglets fed a common basal diet (I); IUGR weaned piglets fed a common basal diet supplemented with 0.1% DMG-Na (ID). They were slaughtered at 49 days of age to collect the serum and LM samples. Compared with the N group, the growth performance, LM structure, serum, and, within the LM, mitochondrial redox status, mitochondrial respiratory chain complex activity, energy metabolites, redox status-related, cell adhesion-related, and mitochondrial function-related gene expression, and protein expression deteriorated in group I (P < 0.05). The ID group showed improved growth performance, LM structure, serum, and, within the LM, mitochondrial redox status, mitochondrial respiratory chain complex activity, energy metabolites, redox status-related, cell adhesion-related, and mitochondrial function-related gene expression, and protein expression compared with those in the I group (P < 0.05). The above results indicated that the DMG-Na treatment could improve the LM redox status and mitochondrial function in IUGR weaned piglets via the Nuclear factor erythroid 2-related factor 2 (Nrf2)/ Sirtuin 1 (SIRT1)/ Peroxisome proliferator-activated receptorγcoactivator-1α (PGC1α) network, thus improving their growth performance.

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Abstract P608: Obesity Induced Hypertension Exacerbated Through Upregulation Of Renal Naci Cotransporter, Reversed By Increasing Pgc-1α-ho-1 Gene Expression To Restore Mitochondrial Function

Hypertension ◽

10.1161/hyp.68.suppl_1.p608 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

David Bamshad ◽

Jian Cao ◽

Joseph Schragenheim ◽

Charles T Stier ◽

Nader G Abraham

Keyword(s):

Mitochondrial Dysfunction ◽

Mitochondrial Biogenesis ◽

Mitochondrial Function ◽

Sodium Excretion ◽

Leptin Receptor ◽

Insulin Receptors ◽

Urinary Sodium Excretion ◽

Induced Hypertension ◽

Group A ◽

Group B

Introduction: Hypertension caused by chronic obesity as a result of high calorie food intake or in leptin receptor deficient db/db mice may be linked to mitochondrial dysfunction. Previously we and others have shown that an epoxyeicosatrienoic acid agonist (EET-A), reduced adiposity and ROS resulting in normalization of BP by unknown mechanisms. We hypothesize that EET-A will attenuate BP by restoring mitochondrial function through increasing the PGC-1α-HO-1 axis and increasing urinary sodium excretion by downregulating NCC channels. Methods: Db/db mice at 16-wks of age were divided into 3 treatment groups and for an additional 16-wks received: A) control, B) EET-A 1.5mg/100g BW i.p. 2x/week and C) EET-A and lentiviral (Ln)- PGC-1α shRNA (to suppress PGC-1α protein). Oxygen consumption (VO 2 ), visceral fat and blood glucose were determined. Additionally, renal tissues were harvested to measure the type 2 Na-K-Cl cotransporters (NKCC2), epithelial Na channels- (ENaC), NaCl cotransporters (NCC), PGC-1α, HO-1, insulin receptors, and mitochondrial biogenesis markers. Results: At the conclusion of 32 weeks: Group A, developed hypertension and presented with decreased urinary Na excretion, decreased VO 2 , decreased downstream PGC-1α signaling, and mitochondrial dysfunction. There were increased levels of NCCs but not of NKCC2s or ENaCs. Renal PGC-1α, HO-1, pAMPK, and mitochondrial fusion protein Mfn 1/2, and Opa1 were decreased, p<0.05. Group B, exhibited restoration of renal levels of PGC-1α, HO-1, pAMPK, and mitochondrial biogenesis proteins Mfn 1/2 and Opa1. NCC expression was reduced and was associated with an increase in urinary Na excretion; (p<0.05). The beneficial effect of EET-A observed in group B was suppressed in group C using Ln- PGC-1α shRNA which suppressed PGC-1α expression in renal tissue > 50% and was accompanied by the onset of even more severe suppression of urinary Na excretion than in Group A. Conclusion: Treatment of obese mice with EET-agonists leads to the recruitment of PGC-1α-HO-1 which enhances mitochondrial function and induces the downregulation of NCC channels and increased sodium excretion. EET may serve as a powerful therapeutic agent for the treatment of obesity induced hypertension.

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Modulation of energy metabolism and mitochondrial biogenesis by a novel proteoglycan fromGanoderma lucidum

RSC Advances ◽

10.1039/c8ra09482a ◽

2019 ◽

Vol 9 (5) ◽

pp. 2591-2598 ◽

Cited By ~ 1

Author(s):

Zhou Yang ◽

Zeng Zhang ◽

Juan Zhao ◽

Yanming He ◽

Hongjie Yang ◽

...

Keyword(s):

Insulin Resistance ◽

Energy Metabolism ◽

Mitochondrial Dysfunction ◽

Mitochondrial Biogenesis ◽

Ganoderma Lucidum

In this study we first focused on the effects of a novel proteoglycan extracted fromGanoderma lucidum(FYGL) on mitochondrial biogenesis, because mitochondrial dysfunction is highly related to insulin resistance.

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