Energetic dysfunction in sepsis: a narrative review

Preau, Sébastien; Vodovar, Dominique; Jung, Boris; Lancel, Steve; Zafrani, Lara; Flatres, Aurelien; Oualha, Mehdi; Voiriot, Guillaume; Jouan, Youenn; Joffre, Jérémie; Huel, Fabrice; Prost, Nicolas de; Silva, Stein; Azabou, Éric; Radermacher, Peter

doi:10.1186/s13613-021-00893-7

Cited by 74 publications

(73 citation statements)

References 260 publications

(360 reference statements)

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“…Given that sepsis is characterized by both systemic and organ-specific metabolic changes [ 53 ], we performed an extensive lipidomic analysis. As seen in Table 3 , a similar pattern of increase was observed regarding carnitine, glycerol, lactate, and total concentration of examined FFAs in the liver, kidneys, and heart.…”

Section: Resultsmentioning

confidence: 99%

The Effects of a Meldonium Pre-Treatment on the Course of the Faecal-Induced Sepsis in Rats

Đurašević

Ružičić

Lakić

et al. 2021

IJMS

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Sepsis is a life-threatening condition caused by the dysregulated and overwhelming response to infection, accompanied by an exaggerated pro-inflammatory state and lipid metabolism disturbance leading to sequential organ failure. Meldonium is an anti-ischemic and anti-inflammatory agent which negatively interferes with lipid metabolism by shifting energy production from fatty acid oxidation to glycolysis, as a less oxygen-demanding pathway. Thus, we investigated the effects of a four-week meldonium pre-treatment on faecal-induced sepsis in Sprague-Dawley male rats. Surprisingly, under septic conditions, meldonium increased animal mortality rate compared with the meldonium non-treated group. However, analysis of the tissue oxidative status did not provide support for the detrimental effects of meldonium, nor did the analysis of the tissue inflammatory status showing anti-inflammatory, anti-apoptotic, and anti-necrotic effects of meldonium. After performing tissue lipidomic analysis, we concluded that the potential cause of the meldonium harmful effect is to be found in the overall decreased lipid metabolism. The present study underlines the importance of uninterrupted energy production in sepsis, closely drawing attention to the possible harmful effects of lipid-mobilization impairment caused by certain therapeutics. This could lead to the much-needed revision of the existing guidelines in the clinical treatment of sepsis while paving the way for discovering new therapeutic approaches.

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Section: Resultsmentioning

confidence: 99%

The Effects of a Meldonium Pre-Treatment on the Course of the Faecal-Induced Sepsis in Rats

Đurašević

Ružičić

Lakić

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Other sepsis-related metabolic disorders include fatty acid/amino acid metabolism disorders, anaerobic metabolism, oxidative stress, and abnormalities in energy metabolism. Mitochondria are the power plants of cells that produce adenosine triphosphate (ATP) via the tricarboxylic acid (TCA) cycle and maintain cellular function ( 31 ). Mitochondrial dysfunction leads to the generation of large amounts of reactive oxygen species (ROS) and can induce cell death (e.g., mitoptosis), which plays an important role in the mechanism underlying the pathogenesis of sepsis ( 31 ).…”

Section: Pathophysiological Mechanisms Of Sepsismentioning

confidence: 99%

“…Mitochondria are the power plants of cells that produce adenosine triphosphate (ATP) via the tricarboxylic acid (TCA) cycle and maintain cellular function ( 31 ). Mitochondrial dysfunction leads to the generation of large amounts of reactive oxygen species (ROS) and can induce cell death (e.g., mitoptosis), which plays an important role in the mechanism underlying the pathogenesis of sepsis ( 31 ). Notably, glucose metabolism pathways, including glycolysis, the TCA cycle, and oxidative phosphorylation (OXPHOS), are closely related to the function of immune cells (i.e., immune metabolism) ( 32 ).…”

Section: Pathophysiological Mechanisms Of Sepsismentioning

confidence: 99%

Evaluation of the Molecular Mechanisms of Sepsis Using Proteomics

Chen

Ding

2021

Front. Immunol.

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Sepsis is a complex syndrome promoted by pathogenic and host factors; it is characterized by dysregulated host responses and multiple organ dysfunction, which can lead to death. However, its underlying molecular mechanisms remain unknown. Proteomics, as a biotechnology research area in the post-genomic era, paves the way for large-scale protein characterization. With the rapid development of proteomics technology, various approaches can be used to monitor proteome changes and identify differentially expressed proteins in sepsis, which may help to understand the pathophysiological process of sepsis. Although previous reports have summarized proteomics-related data on the diagnosis of sepsis and sepsis-related biomarkers, the present review aims to comprehensively summarize the available literature concerning “sepsis”, “proteomics”, “cecal ligation and puncture”, “lipopolysaccharide”, and “post-translational modifications” in relation to proteomics research to provide novel insights into the molecular mechanisms of sepsis.

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“…Cardiomyocytes are rich in mitochondria, especially in the areas between sarcomeres and the subsarcolemma ( 21 ). As the energy metabolism centres of cells ( 22 ), mitochondria function to generate energy through oxidative phosphorylation (OXPHOS) ( 23 ). Of the important mechanisms of septic cardiomyopathy, the specific mechanism of mitochondrial dysfunction is under debate.…”

Section: Mechanisms Of Mitochondrial Dysfunction In Septic Cardiomyopathymentioning

confidence: 99%

Roles of LncRNAs in Regulating Mitochondrial Dysfunction in Septic Cardiomyopathy

Liu

Wang

2021

Front. Immunol.

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Sepsis is an abnormal systemic inflammatory response of the host immune system to infection and can lead to fatal multiorgan dysfunction syndrome. Epidemiological studies have shown that approximately 10-70% of sepsis cases can lead to septic cardiomyopathy. Since the pathogenesis of septic cardiomyopathy is not clear, it is difficult for medical doctors to treat the disease. Therefore, finding effective interventions to prevent and reduce myocardial damage in septic cardiomyopathy is clinically significant. Epigenetics is the study of stable genetic phenotype inheritance that does not involve changing gene sequences. Epigenetic inheritance is affected by both gene and environmental regulation. Epigenetic studies focus on the modification and influence of chromatin structure, mainly including chromatin remodelling, DNA methylation, histone modification and noncoding RNA (ncRNA)-related mechanisms. Recently, long ncRNA (lncRNA)-related mechanisms have been the focus of epigenetic studies. LncRNAs are expected to become important targets to prevent, diagnose and treat human diseases. As the energy metabolism centre of cells, mitochondria are important targets in septic cardiomyopathy. Intervention measures to prevent and treat mitochondrial damage are of great significance for improving the prognosis of septic cardiomyopathy. LncRNAs play important roles in life activities. Recently, studies have focused on the involvement of lncRNAs in regulating mitochondrial dysfunction. However, few studies have revealed the involvement of lncRNAs in regulating mitochondrial dysfunction in septic cardiomyopathy. In this article, we briefly review recent research in this area.

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Energetic dysfunction in sepsis: a narrative review

Cited by 74 publications

References 260 publications

The Effects of a Meldonium Pre-Treatment on the Course of the Faecal-Induced Sepsis in Rats

The Effects of a Meldonium Pre-Treatment on the Course of the Faecal-Induced Sepsis in Rats

Evaluation of the Molecular Mechanisms of Sepsis Using Proteomics

Roles of LncRNAs in Regulating Mitochondrial Dysfunction in Septic Cardiomyopathy

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