Energy substrate metabolism and oxidative stress in metabolic cardiomyopathy

Chen, Ze; Jin, Zhaoxia; Cai, Jingjing; Li, Ruyan; Deng, Ke‐Qiong; Ji, Yan‐Xiao; Lei, Fang; Li, Huo‐Ping; Lu, Zhibing; Li, Hong Liang

doi:10.1007/s00109-022-02269-1

Cited by 20 publications

(12 citation statements)

References 200 publications

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“…Melatonin and its metabolites are all highly efficient scavengers of ROS [ 87 , 231 , 232 ]. This is particularly important at the mitochondrial level, since partially reduced oxygen derivatives are abundantly produced in these organelles and provide the basis for massive free radical damage that occurs when electrons leak from the electron transport chain [ 233 ]. To compensate for the large number of oxidizing agents produced in these organelles, mitochondria, as recently discovered, also generate their own melatonin [ 33 , 45 ] to aid in combatting the massive molecular destruction that would otherwise occur.…”

Section: Discussionmentioning

confidence: 99%

Aging-Related Ovarian Failure and Infertility: Melatonin to the Rescue

et al. 2023

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Aging has a major detrimental effect on the optimal function of the ovary with changes in this organ preceding the age-related deterioration in other tissues, with the middle-aged shutdown leading to infertility. Reduced fertility and consequent inability to conceive by women in present-day societies who choose to have children later in life leads to increased frustration. Melatonin is known to have anti-aging properties related to its antioxidant and anti-inflammatory actions. Its higher follicular fluid levels relative to blood concentrations and its likely synthesis in the oocyte, granulosa, and luteal cells suggest that it is optimally positioned to interfere with age-associated deterioration of the ovary. Additionally, the end of the female reproductive span coincides with a significant reduction in endogenous melatonin levels. Thus, the aims are to review the literature indicating melatonin production in mitochondria of oocytes, granulosa cells, and luteal cells, identify the multiple processes underlying changes in the ovary, especially late in the cessation of the reproductive life span, summarize the physiological and molecular actions of melatonin in the maintenance of normal ovaries and in the aging ovaries, and integrate the acquired information into an explanation for considering melatonin in the treatment of age-related infertility. Use of supplemental melatonin may help preserve fertility later in life and alleviate frustration in women delaying childbearing age, reduce the necessity of in vitro fertilization–embryo transfer (IVF-ET) procedures, and help solve the progressively increasing problem of non-aging-related infertility in women throughout their reproductive life span. While additional research is needed to fully understand the effects of melatonin supplementation on potentially enhancing fertility, studies published to date suggest it may be a promising option for those struggling with infertility.

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Section: Discussionmentioning

confidence: 99%

Aging-Related Ovarian Failure and Infertility: Melatonin to the Rescue

et al. 2023

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“…Recent studies have shown that the process of fatty acid oxidation is accompanied by the production of NADPH ( 29 – 31 ), which is an important antioxidant molecule that maintains glutathione and thioredoxin in the reduced state and is involved in the regulation of intracellular oxidative stress. We have therefore also focused on the effect of Tcea3 on oxidative stress in PE-induced cardiomyocytes.…”

Section: Discussionmentioning

confidence: 99%

Identify Tcea3 as a novel anti-cardiomyocyte hypertrophy gene involved in fatty acid oxidation and oxidative stress

Cen

Qiu

et al. 2023

Front. Cardiovasc. Med.

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BackgroundChronic pressure overload triggers pathological cardiac hypertrophy that eventually leads to heart failure. Effective biomarkers and therapeutic targets for heart failure remain to be defined. The aim of this study is to identify key genes associated with pathological cardiac hypertrophy by combining bioinformatics analyses with molecular biology experiments.MethodsComprehensive bioinformatics tools were used to screen genes related to pressure overload-induced cardiac hypertrophy. We identified differentially expressed genes (DEGs) by overlapping three Gene Expression Omnibus (GEO) datasets (GSE5500, GSE1621, and GSE36074). Correlation analysis and BioGPS online tool were used to detect the genes of interest. A mouse model of cardiac remodeling induced by transverse aortic constriction (TAC) was established to verify the expression of the interest gene during cardiac remodeling by RT-PCR and western blot. By using RNA interference technology, the effect of transcription elongation factor A3 (Tcea3) silencing on PE-induced hypertrophy of neonatal rat ventricular myocytes (NRVMs) was detected. Next, gene set enrichment analysis (GSEA) and the online tool ARCHS4 were used to predict the possible signaling pathways, and the fatty acid oxidation relevant pathways were enriched and then verified in NRVMs. Furthermore, the changes of long-chain fatty acid respiration in NRVMs were detected using the Seahorse XFe24 Analyzer. Finally, MitoSOX staining was used to detect the effect of Tcea3 on mitochondrial oxidative stress, and the contents of NADP(H) and GSH/GSSG were detected by relevant kits.ResultsA total of 95 DEGs were identified and Tcea3 was negatively correlated with Nppa, Nppb and Myh7. The expression level of Tcea3 was downregulated during cardiac remodeling both in vivo and in vitro. Knockdown of Tcea3 aggravated cardiomyocyte hypertrophy induced by PE in NRVMs. GSEA and online tool ARCHS4 predict Tcea3 involved in fatty acid oxidation (FAO). Subsequently, RT-PCR results showed that knockdown of Tcea3 up-regulated Ces1d and Pla2g5 mRNA expression levels. In PE induced cardiomyocyte hypertrophy, Tcea3 silencing results in decreased fatty acid utilization, decreased ATP synthesis and increased mitochondrial oxidative stress.ConclusionOur study identifies Tcea3 as a novel anti-cardiac remodeling target by regulating FAO and governing mitochondrial oxidative stress.

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“…Reinforcing this idea, lower levels of an acyl-coenzyme A, which is the form in which fatty acids are used in mitochondrial beta-oxidation, were detected in non-dippers. Mitochondrial dysfunction is a major source of ROS production [68]. ROS can act as signaling molecules that play important regulatory roles in a plethora of physiological processes [69], potentially including the circadian regulation of BP.…”

Section: Discussionmentioning

confidence: 99%

Metabolipidomic Analysis in Patients with Obstructive Sleep Apnea Discloses a Circulating Metabotype of Non-Dipping Blood Pressure

Pinilla,

Benítez,

Gracia-Lavedan

et al. 2023

Antioxidants

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A non-dipping blood pressure (BP) pattern, which is frequently present in patients with obstructive sleep apnea (OSA), confers high cardiovascular risk. The mechanisms connecting these two conditions remain unclear. In the present study we performed a comprehensive analysis of the blood metabolipidome that aims to provide new insights into the molecular link between OSA and the dysregulation of circadian BP rhythmicity. This was an observational prospective longitudinal study involving adults with suspected OSA who were subjected to full polysomnography (PSG). Patients with an apnea–hypopnea index ≥ 5 events/h were included. Fasting plasma samples were obtained the morning after PSG. Based on the dipping ratio (DR; ratio of night/day BP values) measured via 24 h ambulatory BP monitoring, two groups were established: dippers (DR ≤ 0.9) and non-dippers (DR > 0.9). Treatment recommendations for OSA followed the clinical guidelines. Untargeted metabolomic and lipidomic analyses were performed in plasma samples via liquid chromatography–tandem mass spectrometry. Non-dipper patients represented 53.7% of the cohort (88/164 patients). A set of 31 metabolic species and 13 lipidic species were differentially detected between OSA patients who present a physiologic nocturnal BP decrease and those with abnormal BP dipping. Among the 44 differentially abundant plasma compounds, 25 were putatively identified, notably glycerophospholipids, glycolipids, sterols, and fatty acid derivates. Multivariate analysis defined a specific metabotype of non-dipping BP, which showed a significant dose-response relationship with PSG parameters of OSA severity, and with BP dipping changes after 6 months of OSA treatment with continuous positive airway pressure (CPAP). Bioinformatic analyses revealed that the identified metabolipidomic profile was found to be implicated in multiple systemic biological pathways, with potential physiopathologic implications for the circadian control of BP among individuals with OSA.

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Energy substrate metabolism and oxidative stress in metabolic cardiomyopathy

Cited by 20 publications

References 200 publications

Aging-Related Ovarian Failure and Infertility: Melatonin to the Rescue

Aging-Related Ovarian Failure and Infertility: Melatonin to the Rescue

Identify Tcea3 as a novel anti-cardiomyocyte hypertrophy gene involved in fatty acid oxidation and oxidative stress

Metabolipidomic Analysis in Patients with Obstructive Sleep Apnea Discloses a Circulating Metabotype of Non-Dipping Blood Pressure

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