Hypoxia-triggered O-GlcNAcylation in the brain drives the glutamate–glutamine cycle and reduces sensitivity to sevoflurane in mice

He, Qinqin; Yang, Man; Huang, Jing; Wu, Wei; Tang, Kuo; Yong, Zhang; Zhou, Jian; Ou, Wei; Liang, Yu; Lu, Peilin; Zuo, Yunxia; Yu, Hai; Li, Tao

doi:10.1016/j.bja.2022.06.041

Cited by 9 publications

(4 citation statements)

References 35 publications

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“…As a consequence, multiple enzymes catalyzing the TCA cycle were downregulated in sarcopenia, leading to reduced levels of TCA metabolites. Moreover, we observed significant defects in mitochondrial structure and quantity, which resulted in reduced oxidative phosphorylation and increased energetic compromise (45)(46)(47). Pathway analysis indicate that oxidative phosphorylation may be altered during the early stages of sarcopenia.…”

Section: Discussionmentioning

confidence: 85%

Integrated Multi-Omics Analysis Identifies Disrupted Branched-Chain Amino Acid Catabolism as Causal for Sarcopenia

Zhao

Zuo

et al. 2023

Preprint

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Sarcopenia is a geriatric skeletal muscle disorder with a gradual loss of skeletal muscle mass and function. Despite its prevalence, the underlying mechanisms of sarcopenia are not yet fully understood, and there are currently no approved treatments. In this study, we conduct a comprehensive analysis of the molecular and metabolic signatures of skeletal muscle in early and late stages of sarcopenia using multi-omics approaches. We found substantial metabolic and mitochondrial dysfunction in sarcopenia. Our results reveal that disrupted BCAA catabolism is a prominent pathway in sarcopenia, which leads to BCAA accumulation and decreased muscle strength and mass. Machine learning analysis further supports the causal role of BCAA catabolic dysfunction in sarcopenia. We further validate our results using separate cohorts of sarcopenia patients and muscle-specific Ppm1k knockout mice. The study highlights the importance of improving BCAA catabolism as a potential strategy for slowing down the progression of sarcopenia.

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Section: Discussionmentioning

confidence: 85%

Integrated Multi-Omics Analysis Identifies Disrupted Branched-Chain Amino Acid Catabolism as Causal for Sarcopenia

Zhao

Zuo

et al. 2023

Preprint

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“…UDP-GlcNAc then provides O-linked β-N-acetylglucosamine (O-GlcNAc) for posttranslational modification, playing an important role in physiology and pathology. [73,74] Increasing evidence suggests that abnormal cardiac O-GlcNAc signaling mediates the adverse effects of diabetes on the heart. [75] PI3K and AKT are modified by O-GlcNAc, impairing the structural and functional characteristics of the diabetic heart.…”

Section: Altered Fuel Preference and Cardiac Energetics In Diabetic C...mentioning

confidence: 99%

Mitochondrial energy metabolism in diabetic cardiomyopathy: Physiological adaption, pathogenesis, and therapeutic targets

Ye,

Han,

Xie

et al. 2024

Chinese Medical Journal

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Diabetic cardiomyopathy is defined as abnormal structure and function of the heart in the setting of diabetes, which could eventually develop heart failure and leads to the death of the patients. Although blood glucose control and medications to heart failure show beneficial effects on this disease, there is currently no specific treatment for diabetic cardiomyopathy. Over the past few decades, the pathophysiology of diabetic cardiomyopathy has been extensively studied, and an increasing number of studies pinpoint that impaired mitochondrial energy metabolism is a key mediator as well as a therapeutic target. In this review, we summarize the latest research in the field of diabetic cardiomyopathy, focusing on mitochondrial damage and adaptation, altered energy substrates, and potential therapeutic targets. A better understanding of the mitochondrial energy metabolism in diabetic cardiomyopathy may help to gain more mechanistic insights and generate more precise mitochondria-oriented therapies to treat this disease.

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“…[6][7][8][9][10][11][12][13][14][15] Sarcopenia and CVDs share several common risk factors, such as lack of physical activity, up-regulation of inflammatory factors, mitochondrial dysfunction, oxidative stress, hormone changes and low muscle blood. 16,17 The deficiency and deterioration of cardiac function affect the blood flow and metabolism of the myocardium and skeletal muscle. Skeletal muscle is one of the important metabolic and endocrine organs, and thus, skeletal muscle atrophy caused by sarcopenia will aggravate CVDs.…”

Section: Introductionmentioning

confidence: 99%

“…With the gradual development and renewal of the consensus on sarcopenia, more and more studies have discovered the relationship between sarcopenia and CVDs, such as heart failure (HF), ischaemic heart disease (IHD), coronary artery disease (CAD), congenital heart disease (CHD) and cardiac arrhythmia (CA) 6–15 . Sarcopenia and CVDs share several common risk factors, such as lack of physical activity, up‐regulation of inflammatory factors, mitochondrial dysfunction, oxidative stress, hormone changes and low muscle blood 16,17 . The deficiency and deterioration of cardiac function affect the blood flow and metabolism of the myocardium and skeletal muscle.…”

Section: Introductionmentioning

confidence: 99%

Sarcopenia and cardiovascular diseases: A systematic review and meta‐analysis

Zuo

Tang

et al. 2023

J cachexia sarcopenia muscle

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Sarcopenia is an age‐related disease and is often accompanied by other diseases. Now, many studies have shown that cardiovascular diseases (CVDs) may raise the incidence rate of sarcopenia. Therefore, the purpose of this study was to conduct a systematic review and meta‐analysis to investigate the prevalence of sarcopenia in patients with CVDs compared with the general population, defined as relatively healthy non‐hospitalized subjects. The databases of PubMed, Embase, Medline and Web of Science were searched for eligible studies published up to 12 November 2022. Two assessment tools were used to evaluate study quality and the risk of bias. Statistical analysis was conducted using STATA 14.0 and R Version 4.1.2. Thirty‐eight out of the 89 629 articles retrieved were included in our review. The prevalence of sarcopenia ranged from 10.1% to 68.9% in patients with CVDs, and the pooled prevalence was 35% (95% confidence interval [95% CI]: 28–42%). The pooled prevalence of sarcopenia was 32% (95% CI: 23–41%) in patients with chronic heart failure (CHF), 61% (95% CI: 49–72%) in patients with acute decompensated heart failure (ADHF), 43% (95% CI: 2–85%) in patients with coronary artery disease, 30% (95% CI: 25–35%) in patients with cardiac arrhythmia (CA), 35% (95% CI: 10–59%) in patients with congenital heart disease and 12% (95% CI: 7–17%) in patients with unclassed CVDs. However, in the general population, the prevalence of sarcopenia varied from 2.9% to 28.6% and the pooled prevalence was 13% (95% CI: 9–17%), suggesting that the prevalence of sarcopenia in patients with CVDs was about twice compared with the general population. The prevalence of sarcopenia was significantly higher only in patients with ADHF, CHF and CA compared with the general population. There is a positive correlation between CVDs and sarcopenia. The prevalence of sarcopenia is higher in patients with CVDs than that in the general population. With global aging, sarcopenia has brought a heavy burden to individuals and society. Therefore, it is important to identify the populations with high‐risk or probable sarcopenia in order to do an early intervention, such as exercise, to counteract or slow down the progress of sarcopenia.

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Hypoxia-triggered O-GlcNAcylation in the brain drives the glutamate–glutamine cycle and reduces sensitivity to sevoflurane in mice

Cited by 9 publications

References 35 publications

Integrated Multi-Omics Analysis Identifies Disrupted Branched-Chain Amino Acid Catabolism as Causal for Sarcopenia

Integrated Multi-Omics Analysis Identifies Disrupted Branched-Chain Amino Acid Catabolism as Causal for Sarcopenia

Mitochondrial energy metabolism in diabetic cardiomyopathy: Physiological adaption, pathogenesis, and therapeutic targets

Sarcopenia and cardiovascular diseases: A systematic review and meta‐analysis

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