Warburg revisited: lessons for innate immunity and sepsis

Srivastava, Anup; Mannam, Praveen

doi:10.3389/fphys.2015.00070

Cited by 47 publications

(35 citation statements)

References 16 publications

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“…In later stages oxidation of fatty acids may also be impaired, as reflected in elevated serum levels of lipoproteins, free fatty acids and triglycerides. Glycolysis is favored over oxidative phosphorylation despite adequate oxygen availability ("aerobic glycolysis", sometimes called the Warburg Effect) [206][207][208]. There is accelerated catabolism of skeletal muscle and perhaps smooth muscle as well [209].…”

Section: Basic/translational Science What Mechanisms Underlie Sepsis-mentioning

confidence: 99%

Surviving sepsis campaign: research priorities for sepsis and septic shock

et al. 2018

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Objective: To identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock.Design: A consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations.Methods: Each committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (ESM 1 -supplemental table 1) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire committee also voted on top priorities across all subgroups except for basic/translational science. Results:The Surviving Sepsis Research Committee provides 26 priorities for sepsis and septic shock. Of these, the top six clinical priorities were identified and include the following questions: (1) can targeted/personalized/precision medicine approaches determine which therapies will work for which patients at which times?; (2) what are ideal endpoints for volume resuscitation and how should volume resuscitation be titrated?; (3) should rapid diagnostic tests be implemented in clinical practice?; (4) should empiric antibiotic combination therapy be used in sepsis or septic shock?; (5) what are the predictors of sepsis long-term morbidity and mortality?; and (6) what information identifies organ dysfunction?Conclusions: While the Surviving Sepsis Campaign guidelines give multiple recommendations on the treatment of sepsis, significant knowledge gaps remain, both in bedside issues directly applicable to clinicians, as well as understanding the fundamental mechanisms underlying the development and progression of sepsis. The priorities identified represent a roadmap for research in sepsis and septic shock.

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Section: Basic/translational Science What Mechanisms Underlie Sepsis-mentioning

confidence: 99%

Surviving sepsis campaign: research priorities for sepsis and septic shock

et al. 2018

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“…Along with these differences in cytokine production, a clear difference in cellular metabolism can be observed [5]. Upon activation, monocytes become hyperinflammatory, and glycolysis is up-regulated, resulting in increased lactate production through a Hif1adependent pathway that up-regulates expression of GLUT1, PFK, and PDK [20][21][22][23][24][25][26]. Likewise, LPS-stimulated BMDM shows an increase in GLUT1, HK3, third isoform of human 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, phosphoglycerate mutase 2, and enolase 2 expression [27,28], and this has been shown to contribute to an increased IL-1b and IL-6 production [27].…”

Section: Shifts In Glycolysismentioning

confidence: 99%

Cellular metabolism of myeloid cells in sepsis

Arts

Gresnigt

Joosten

et al. 2016

Journal of Leukocyte Biology

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In recent years, it has become appreciated that immune cells have different metabolic profiles depending on their activation status. During sepsis, circulating leukocytes go through a hyperinflammatory state, which can be accompanied or followed by defective antimicrobial defenses (also described as immune tolerance or paralysis). In this review, the modulation of different cellular metabolic pathways during sepsis in monocytes and macrophages will be discussed. Glycolysis is studied extensively in sepsis and is up-regulated in hyperinflammatory cells, whereas in immune tolerance, it is often down-regulated. Few data are available on other metabolic pathways in immune cells from patients with sepsis. The pentose phosphate pathway is up-regulated during acute hyperinflammatory responses, whereas fatty acid β-oxidation is increased later during sepsis and is associated with an anti-inflammatory (M2) phenotype of macrophages. Within the amino acid metabolism we will discuss the most studied metabolites. Collectively, these data argue that exploration of the immunometabolic pathways in sepsis is an important area of research, and the targeting of metabolic pathways may represent a promising novel strategy as a therapy of sepsis.

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“…This energetic deregulation effect favours the activation of aerobic glycolysis to provide the required ATP turnover rate. This situation has been observed in various diseases enumerated in this review such as in cancer . Furthermore, atmospheric pressure will affect molecular distance, another phenomenon that can surely play on cell metabolism, also affecting the enzyme‐substrate complex establishment and efficiency .…”

Section: Cells Sense Mechanical and Osmotic Forcesmentioning

confidence: 70%

“…Increased osmotic pressure results in a transient Warburg effect, a partial and reversible inhibition of the mitochondrial activity . The sequence and list of the effects of a high osmotic environment on cell behaviour are illustrated in Fig.…”

Section: Physical Forces Control the Mitochondriamentioning

confidence: 99%

Physical forces modulate cell differentiation and proliferation processes

Schwartz

Moreira

Jolicœur

2017

J Cellular Molecular Medi

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Currently, the predominant hypothesis explains cellular differentiation and behaviour as an essentially genetically driven intracellular process, suggesting a gene‐centrism paradigm. However, although many living species genetic has now been described, there is still a large gap between the genetic information interpretation and cell behaviour prediction. Indeed, the physical mechanisms underlying the cell differentiation and proliferation, which are now known or suspected to guide such as the flow of energy through cells and tissues, have been often overlooked. We thus here propose a complementary conceptual framework towards the development of an energy‐oriented classification of cell properties, that is, a mitochondria‐centrism hypothesis based on physical forces‐driven principles. A literature review on the physical–biological interactions in a number of various biological processes is analysed from the point of view of the fluid and solid mechanics, electricity and thermodynamics. There is consistent evidence that physical forces control cell proliferation and differentiation. We propose that physical forces interfere with the cell metabolism mostly at the level of the mitochondria, which in turn control gene expression. The present perspective points towards a paradigm shift complement in biology.

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Warburg revisited: lessons for innate immunity and sepsis

Cited by 47 publications

References 16 publications

Surviving sepsis campaign: research priorities for sepsis and septic shock

Surviving sepsis campaign: research priorities for sepsis and septic shock

Cellular metabolism of myeloid cells in sepsis

Physical forces modulate cell differentiation and proliferation processes

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