SFC/EM: Capacidad reducida del SI para satisfacer la demanda de energía
Publicado: 02 Ago 2018, 22:32
Científicos de la universidad de Griffth en Australia han encontrado una reducción significativa de la reserva glucolítica en las células NK de los enfermos de SFC/EM, comparado con los controles sanos.
"Estos hallazgos sugieren que las células NK en reposo de los enfermos de SFC/EM tienen una capacidad reducida para incrementar el flujo glucolítico y responder a la demanda energética necesaria para la producción de ATP (la adenosina trifosfato o ATP es la energía que las células necesitan). Por ello, las reservas glucólicas reducidas que hemos identificado en células NK en reposo aisladas deberían ser investigadas en profundidad para ayudar en la comprensión de la patogénesis del SFC/EM"
La glucólisis es una vía metabólica fundamental que es crítica para la producción de energía. El flujo glicolítico, o la velocidad a la que las moléculas proceden a través de la vía glucolítica, está estrechamente regulado en respuesta al entorno celular, según el Journal of Biological Chemistry.
El estudio dice que no está claro si la causa de esta reducción es intracelular o extracelular.
El estudio "Reducción de la reserva glucolítica en células asesinas naturales aisladas de pacientes con encefalomielitis miálgica / síndrome de fatiga crónica: una investigación preliminar" se publicó en el Asian Pacific Journal of Allergy and Immunology, julio de 2018.
--- Es un estudio pequeño, que esperemos alguien repita con una base amplia, lo que permitiría no sólo comprobar éste hallazgo, sino también reforzar o refutar otros relativos a defectos en la respiración mitocondrial de enfermos de SFC/EM. Como siempre, esperemos que alguien recoja el guante...
“These findings suggest resting NK cells from ME/CFS patients have reduced ability to increase glycolytic flux to respond to high energetic demands for ATP production (adenosine triphosphate or ATP is a usable form of energy for cells). Hence, the reduced glycolytic reserves we have identified in isolated resting isolated NK cells should be further investigated to assist in understanding ME/CFS pathogenesis.”
Glycolysis is a fundamental metabolic pathway that is critical for the production of energy. Glycolytic flux, or the rate at which molecules proceed through the glycolytic pathway, is tightly regulated in response to the cellular environment, according to the Journal of Biological Chemistry.
The study says it is unclear whether the cause of this reduction is intracellular or extracellular.
The study, ‘Reduced glycolytic reserve in isolated natural killer cells from Myalgic encephalomyelitis/chronic fatigue syndrome patients: A preliminary investigation’ was published in the Asian Pacific Journal of Allergy and Immunology, July 2018.
The small study compared six people with ME (meeting the International Consensus Criteria for Myalgic Encephalomyelitis, as well as the Fukuda criteria for chronic fatigue syndrome), with an average age of 50. The authors said a major limitation to this study is sample size and a larger cohort is warranted to confirm the finding.
“The preliminary investigation is the first to report a significant reduction of glycolytic reserve in resting isolated NK cells from ME/CFS patients compared with healthy controls. The novel finding may perhaps postulate NK cells from ME/CFS may have difficulty upregulating glycolysis for effector function in response to immune challenges or during stress.”
Lead author Thao Nguyen of The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland at Griffith University, found there was ‘no significant difference observed in mitochondrial respiration, although the authors noted that other studies have shown ME/CFS reduced mitochondria respiration drives glycolysis to compensate for high energy demands’. The studies are ‘Cellular bioenergetics is impaired in patients with chronic fatigue syndrome’, Tomas et al 2017, ‘Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome’, Fluge et al 2016.
Other Australian researchers at Melbourne University (Armstrong et al 2015) found ‘blood glucose was elevated while blood lactate, urine pyruvate, and urine alanine were reduced indicating an inhibition of glycolysis that may potentially reduce the provision of adequate acetyl-CoA for the citric acid cycle. We propose that amino acids are being increasingly used to provide an adequate carbohydrate source for the citric acid cycle’.
The immune system
The study explains ‘the immune system utilizes energy for pathogen clearance, activation of inflammation and autoimmune responses. The most consistent immunological finding is significantly reduced cytotoxic activity in Natural Killer (NK) cells. Cytotoxicity is desirable to help fight infection and kill transformed cells to prevent diseases but requires high energy consumption. In sickness behavior, the body undergoes energy conservation which priorities the energy towards immune cells to help fight off pathogens through the release of proinflammatory cytokines. Whereas, ME/CFS illness has been suggested to be associated with activation of inflammation and oxidative stress, and yet may not resolve infection’.
An earlier immune study at Griffith University, ‘Longitudinal analysis of immune abnormalities in varying severities of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients’, Hardcastle et al 2015, found ‘severe CFS/ME patients differed from controls and moderate CFS/ME patients over time and expressed significant alterations in iNKT cell phenotypes, CD8+T cell markers, NK cell receptors and γδT cells at 6 months’ so it would be interesting to see if there are further differences between severe and moderate ME patients in future studies.
This study was supported by funding from the Stafford Fox Medical Research Foundation, the Alison Hunter Memorial Foundation, Mason Foundation, Mr Douglas Stutt, Blake Beckett Foundation and Queensland Co-Investment Program.
enlace: https://meaustralia.net/2018/07/25/stud ... e-systems/
"Estos hallazgos sugieren que las células NK en reposo de los enfermos de SFC/EM tienen una capacidad reducida para incrementar el flujo glucolítico y responder a la demanda energética necesaria para la producción de ATP (la adenosina trifosfato o ATP es la energía que las células necesitan). Por ello, las reservas glucólicas reducidas que hemos identificado en células NK en reposo aisladas deberían ser investigadas en profundidad para ayudar en la comprensión de la patogénesis del SFC/EM"
La glucólisis es una vía metabólica fundamental que es crítica para la producción de energía. El flujo glicolítico, o la velocidad a la que las moléculas proceden a través de la vía glucolítica, está estrechamente regulado en respuesta al entorno celular, según el Journal of Biological Chemistry.
El estudio dice que no está claro si la causa de esta reducción es intracelular o extracelular.
El estudio "Reducción de la reserva glucolítica en células asesinas naturales aisladas de pacientes con encefalomielitis miálgica / síndrome de fatiga crónica: una investigación preliminar" se publicó en el Asian Pacific Journal of Allergy and Immunology, julio de 2018.
--- Es un estudio pequeño, que esperemos alguien repita con una base amplia, lo que permitiría no sólo comprobar éste hallazgo, sino también reforzar o refutar otros relativos a defectos en la respiración mitocondrial de enfermos de SFC/EM. Como siempre, esperemos que alguien recoja el guante...
Study finds reduced ability to respond to energy demands in ME patients’ immune systems
Scientists from Australia’s Griffith University found ‘a significant reduction of glycolytic reserve in resting natural killer (NK) cells’ from people with Myalgic Encephalomyelitis (ICC ME) compared with healthy controls.“These findings suggest resting NK cells from ME/CFS patients have reduced ability to increase glycolytic flux to respond to high energetic demands for ATP production (adenosine triphosphate or ATP is a usable form of energy for cells). Hence, the reduced glycolytic reserves we have identified in isolated resting isolated NK cells should be further investigated to assist in understanding ME/CFS pathogenesis.”
Glycolysis is a fundamental metabolic pathway that is critical for the production of energy. Glycolytic flux, or the rate at which molecules proceed through the glycolytic pathway, is tightly regulated in response to the cellular environment, according to the Journal of Biological Chemistry.
The study says it is unclear whether the cause of this reduction is intracellular or extracellular.
The study, ‘Reduced glycolytic reserve in isolated natural killer cells from Myalgic encephalomyelitis/chronic fatigue syndrome patients: A preliminary investigation’ was published in the Asian Pacific Journal of Allergy and Immunology, July 2018.
The small study compared six people with ME (meeting the International Consensus Criteria for Myalgic Encephalomyelitis, as well as the Fukuda criteria for chronic fatigue syndrome), with an average age of 50. The authors said a major limitation to this study is sample size and a larger cohort is warranted to confirm the finding.
“The preliminary investigation is the first to report a significant reduction of glycolytic reserve in resting isolated NK cells from ME/CFS patients compared with healthy controls. The novel finding may perhaps postulate NK cells from ME/CFS may have difficulty upregulating glycolysis for effector function in response to immune challenges or during stress.”
Lead author Thao Nguyen of The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland at Griffith University, found there was ‘no significant difference observed in mitochondrial respiration, although the authors noted that other studies have shown ME/CFS reduced mitochondria respiration drives glycolysis to compensate for high energy demands’. The studies are ‘Cellular bioenergetics is impaired in patients with chronic fatigue syndrome’, Tomas et al 2017, ‘Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome’, Fluge et al 2016.
Other Australian researchers at Melbourne University (Armstrong et al 2015) found ‘blood glucose was elevated while blood lactate, urine pyruvate, and urine alanine were reduced indicating an inhibition of glycolysis that may potentially reduce the provision of adequate acetyl-CoA for the citric acid cycle. We propose that amino acids are being increasingly used to provide an adequate carbohydrate source for the citric acid cycle’.
The immune system
The study explains ‘the immune system utilizes energy for pathogen clearance, activation of inflammation and autoimmune responses. The most consistent immunological finding is significantly reduced cytotoxic activity in Natural Killer (NK) cells. Cytotoxicity is desirable to help fight infection and kill transformed cells to prevent diseases but requires high energy consumption. In sickness behavior, the body undergoes energy conservation which priorities the energy towards immune cells to help fight off pathogens through the release of proinflammatory cytokines. Whereas, ME/CFS illness has been suggested to be associated with activation of inflammation and oxidative stress, and yet may not resolve infection’.
An earlier immune study at Griffith University, ‘Longitudinal analysis of immune abnormalities in varying severities of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients’, Hardcastle et al 2015, found ‘severe CFS/ME patients differed from controls and moderate CFS/ME patients over time and expressed significant alterations in iNKT cell phenotypes, CD8+T cell markers, NK cell receptors and γδT cells at 6 months’ so it would be interesting to see if there are further differences between severe and moderate ME patients in future studies.
This study was supported by funding from the Stafford Fox Medical Research Foundation, the Alison Hunter Memorial Foundation, Mason Foundation, Mr Douglas Stutt, Blake Beckett Foundation and Queensland Co-Investment Program.
enlace: https://meaustralia.net/2018/07/25/stud ... e-systems/