Role of liver AMPK and GCN2 kinases in the control of postprandial protein metabolism in response to mid-term high or low protein intake in mice

Chalvon‐Demersay, Tristan; Gaudichon, Claire; Moro, Joanna; Even, Patrick C.; Khodorova, Nadezda; Piedcoq, Julien; Viollet, Benoı̂t; Avérous, Julien; Maurin, Anne‐Catherine; Tomé, Daniel; Foretz, Marc; Fafournoux, Pierre; Azzout‐Marniche, Dalila

doi:10.1007/s00394-022-02983-z

Cited by 3 publications

(1 citation statement)

References 35 publications

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“…The translation of most mRNAs is reduced as a result of this phosphorylation, but some of them, including activating transcription factor 4 (ATF4), show an increase in translation (Carraro et al, 2010). GCN2/eIF2α/ATF4 plays crucial roles in apoptosis, proliferation, and differentiation, making it a major prospective therapeutic target for the treatment of many diseases (Chalvon‐Demersay et al, 2023; Croucher et al, 2021; Lee et al, 2023). Multiple studies have found that the GCN2‐eIF2α‐ATF4 axis is activated in various hematopoietic diseases, including acute lymphoblastic leukemia, acute myelocytic leukemia, and multiple myeloma (Nwosu et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Nicotinamide riboside intervention alleviates hematopoietic system injury of ionizing radiation‐induced premature aging mice

Li,

Wang,

Dong

et al. 2023

Aging Cell

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Radiotherapy destroys cancer cells and inevitably harms normal human tissues, causing delayed effects of acute radiation exposure (DEARE) and accelerating the aging process in most survivors. However, effective methods for preventing premature aging induced by ionizing radiation are lacking. In this study, the premature aging mice of DEARE model was established after 6 Gy total body irradiation (TBI). Then the therapeutic effects and mechanism of nicotinamide riboside on the premature aging mice were evaluated. The results showed that 6 Gy TBI induced premature aging of the hematopoietic system in mice. Nicotinamide riboside treatment reversed aging spleen phenotypes by inhibiting cellular senescence and ameliorated serum metabolism profiles. Further results demonstrated that nicotinamide riboside supplementation alleviated the myeloid bias of hematopoietic stem cells and temporarily restored the regenerative capacity of hematopoietic stem cells probably by mitigating the reactive oxygen species activated GCN2/eIF2α/ATF4 signaling pathway. The results of this study firstly indicate that nicotinamide riboside shows potential as a DEARE therapeutic agent for radiation‐exposed populations and patients who received radiotherapy.

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Section: Introductionmentioning

confidence: 99%

Nicotinamide riboside intervention alleviates hematopoietic system injury of ionizing radiation‐induced premature aging mice

Li,

Wang,

Dong

et al. 2023

Aging Cell

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Les voies de signalisation régulées par la disponibilité en acides aminés : contrôle de fonctions physiologiques et impacts en santé

Fafournoux

2024

Médecine des Maladies Métaboliques

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GCN2 drives diurnal patterns in the hepatic integrated stress response and maintains circadian rhythms in whole body metabolism during amino acid insufficiency

Levy,

Mirek,

Rodriguez

et al. 2024

American Journal of Physiology-Endocrinology and Metabolism

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Disruptions in circadian rhythms are associated with increased risk of developing metabolic diseases. General control nonderepressible 2 (GCN2), a primary sensor of amino acid insufficiency and activator of the integrated stress response (ISR), has emerged as a conserved regulator of the circadian clock in multiple organisms. The objective of this study was to examine diurnal patterns in hepatic ISR activation in the liver and whole-body rhythms in metabolism. We hypothesized that GCN2 activation cues hepatic ISR signaling over a natural 24 h feeding fasting cycle. To address our objective, wild type (WT) and whole body Gcn2 knockout (GCN2 KO) mice were housed in metabolic cages and provided free access to either a Control or leucine-devoid diet (LeuD) for 8-days in total darkness. On the last day, blood and livers were collected at circadian time (CT) 3 and CT15. In livers of WT mice, GCN2 phosphorylation followed a diurnal pattern that was guided by intracellular branched chain amino acid concentrations (r2=0.93). Feeding LeuD to WT mice increased hepatic ISR activation at CT15 only. Diurnal oscillation in hepatic ISR signaling, the hepatic transcriptome including lipid metabolic genes, and triglyceride concentrations were substantially reduced or absent in GCN2 KO mice. Further, mice lacking GCN2 were unable to maintain circadian rhythms in whole body energy expenditure, respiratory exchange ratio and physical activity when fed LeuD. In conclusion, GCN2 activation functions to maintain diurnal ISR activation in the liver and has a vital role in the mechanisms by which nutrient stress affects whole-body metabolism.

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Role of liver AMPK and GCN2 kinases in the control of postprandial protein metabolism in response to mid-term high or low protein intake in mice

Cited by 3 publications

References 35 publications

Nicotinamide riboside intervention alleviates hematopoietic system injury of ionizing radiation‐induced premature aging mice

Nicotinamide riboside intervention alleviates hematopoietic system injury of ionizing radiation‐induced premature aging mice

Les voies de signalisation régulées par la disponibilité en acides aminés : contrôle de fonctions physiologiques et impacts en santé

GCN2 drives diurnal patterns in the hepatic integrated stress response and maintains circadian rhythms in whole body metabolism during amino acid insufficiency

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