Glucocorticoid-dependent REDD1 expression reduces muscle metabolism to enable adaptation under energetic stress

Britto, Florian; Cortade, Fabienne; Belloum, Yassine; Blaquière, Marine; Gallot, Yann S.; Docquier, Aurélie; Pagano, Allan; Jublanc, Élodie; Bendridi, Nadia; Koechlin-Ramonatxo, Christelle; Chabi, Béatrice; Francaux, Marc; Casas, François; Freyssenet, Damien; Rieusset, Jennifer; Giorgetti‐Peraldi, Sophie; Carnac, Gilles; Ollendorff, Vincent; Favier, F.

doi:10.1186/s12915-018-0525-4

Cited by 35 publications

(77 citation statements)

References 65 publications

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“…During muscle contractions, AMPK activation depends upon exercise intensity (29,37,48). While the exact mechanisms remain to be uncovered, REDD1 protein expression is also enhanced by energetic stress and thus aerobic exercise (7,19,24). REDD1 reduces protein synthesis and alters mitochondrial function in skeletal muscle (6,7).…”

Section: Introductionmentioning

confidence: 99%

“…While the exact mechanisms remain to be uncovered, REDD1 protein expression is also enhanced by energetic stress and thus aerobic exercise (7,19,24). REDD1 reduces protein synthesis and alters mitochondrial function in skeletal muscle (6,7). The effect of REDD1 on mitochondrial activity might originate from its role on endoplasmic reticulum (ER)-mitochondria contact sites (called hereafter MAMs for mitochondria-associated membranes).…”

Section: Introductionmentioning

confidence: 99%

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Endurance exercise decreases protein synthesis and ER-mitochondria contacts in mouse skeletal muscle

Merle

Jollet

Britto

et al. 2019

Journal of Applied Physiology

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Exercise is important to maintain skeletal muscle mass through stimulation of protein synthesis, which is a major ATP-consuming process for cells. However, muscle cells have to face high energy demand during contraction. The present study aimed to investigate protein synthesis regulation during aerobic exercise in mouse hindlimb muscles. Male C57Bl/6J mice ran at 12 m/min for 45 min or at 12 m/min for the first 25 min followed by a progressive increase in velocity up to 20 m/min for the last 20 min. Animals were injected intraperitoneally with 40 nmol/g of body weight of puromycin and euthanized by cervical dislocation immediately after exercise cessation. Analysis of gastrocnemius, plantaris, quadriceps, soleus, and tibialis anterior muscles revealed a decrease in protein translation assessed by puromycin incorporation, without significant differences among muscles or running intensities. The reduction of protein synthesis was associated with a marked inhibition of mammalian target of rapamycin complex 1 (mTORC1)-dependent phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1, a mechanism consistent with reduced translation initiation. A slight activation of AMP-activated protein kinase consecutive to the running session was measured but did not correlate with mTORC1 inhibition. More importantly, exercise resulted in a strong upregulation of regulated in development and DNA damage 1 (REDD1) protein and gene expressions, whereas transcriptional regulation of other recognized exercise-induced genes ( IL-6, kruppel-like factor 15, and regulator of calcineurin 1) did not change. Consistently with the recently discovered role of REDD1 on mitochondria-associated membranes, we observed a decrease in mitochondria-endoplasmic reticulum interaction following exercise. Collectively, these data raise questions concerning the role of mitochondria-associated endoplasmic reticulum membrane disruption in the regulation of muscle proteostasis during exercise and, more generally, in cell adaptation to metabolic stress. NEW & NOTEWORTHY How muscles regulate protein synthesis to cope with the energy demand during contraction is poorly documented. Moreover, it is unknown whether protein translation is differentially affected among mouse hindlimb muscles under different physiological exercise modalities. We showed here that 45 min of running decreases puromycin incorporation similarly in 5 different mouse muscles. This decrease was associated with a strong increase in regulated in development and DNA damage 1 protein expression and a significant disruption of the mitochondria and sarcoplasmic reticulum interaction.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Endurance exercise decreases protein synthesis and ER-mitochondria contacts in mouse skeletal muscle

Merle

Jollet

Britto

et al. 2019

Journal of Applied Physiology

Self Cite

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“…(ATP synthase beta) and mitochondrial DNA (means of NADH dehydrogenase subunit 5 and NADH dehydrogenase subunit 2) were quantified by quantitative real-time polymerase chain reaction(10). Each sample was run in duplicate.…”

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confidence: 99%

Gut bacteria are critical for optimal muscle function: a potential link with glucose homeostasis

Nay

Jollet

Goustard

et al. 2019

American Journal of Physiology-Endocrinology and Metabolism

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189

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Gut microbiota is involved in the development of several chronic diseases, including diabetes, obesity, and cancer, through its interactions with the host organs. It has been suggested that the cross talk between gut microbiota and skeletal muscle plays a role in different pathological conditions, such as intestinal chronic inflammation and cachexia. However, it remains unclear whether gut microbiota directly influences skeletal muscle function. In this work, we studied the impact of gut microbiota modulation on mice skeletal muscle function and investigated the underlying mechanisms. We determined the consequences of gut microbiota depletion after treatment with a mixture of a broad spectrum of antibiotics for 21 days and after 10 days of natural reseeding. We found that, in gut microbiota-depleted mice, running endurance was decreased, as well as the extensor digitorum longus muscle fatigue index in an ex vivo contractile test. Importantly, the muscle endurance capacity was efficiently normalized by natural reseeding. These endurance changes were not related to variation in muscle mass, fiber typology, or mitochondrial function. However, several pertinent glucose metabolism markers, such as ileum gene expression of short fatty acid chain and glucose transporters G protein-coupled receptor 41 and sodium-glucose cotransporter 1 and muscle glycogen level, paralleled the muscle endurance changes observed after treatment with antibiotics for 21 days and reseeding. Because glycogen is a key energetic substrate for prolonged exercise, modulating its muscle availability via gut microbiota represents one potent mechanism that can contribute to the gut microbiota-skeletal muscle axis. Taken together, our results strongly support the hypothesis that gut bacteria are required for host optimal skeletal muscle function.

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“…Therefore, the hypoxia-induced glycogen accumulation may be a protective adaptation of cells for ensuring adequate energy reserve to cope with further hypoxic conditions. During prolonged aerobic activity, a depletion of muscle glycogen often occurs and is correlated with the inability to maintain muscle contraction force (Britto et al, 2018;Ørtenblad et al, 2013). Glycogen stores in skeletal muscles exhibited a dramatic reduction after exercise in both normoxic and hypoxic conditions (Baldwin et al, 1975).…”

Section: Discussionmentioning

confidence: 99%

Assessment of fatigue-related biochemical alterations in a rat swimming model under hypoxia

Shan

Yang

et al. 2019

Journal of Experimental Biology

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It is well known that exercise-induced fatigue is exacerbated following hypoxia exposure and may arise from central and/or peripheral mechanisms. To assess the relative contribution of peripheral and central factors to exercise-induced fatigue under hypoxia, a rat model of fatigue by a bout of exhaustive swimming was established and fatigue-related biochemical changes in normoxic and severe hypoxic conditions were compared. Rats were randomly divided into four groups: normoxia resting (NR), exhaustive swimming (NE), hypoxia resting (HR) and exhaustive swimming (HE). The swimming time to exhaustion with a weight equal to 2.5% of their body weight reduced under hypoxia. There were lower blood lactate levels, lower gastrocnemius pAMPK/AMPK ratios and higher gastrocnemius glycogen contents in the HE than in the NE groups, which all suggested a lower degree of peripheral fatigue in the HE group than in the NE group. Meanwhile, there was a significant increase in striatal 3,4-dihydroxyphenylacetic acid (DOPAC) caused by exhaustive swimming under normoxia, whereas this increase was almost blunted under severe hypoxia, indicating that hypoxia might exacerbate exercise-induced central fatigue. These biochemical changes suggest that from normoxia to severe hypoxia, the relative contribution of peripheral and central factors to exercise-induced fatigue alters, and central fatigue may play a predominant role in the decline in exercise performance under hypoxia.

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Glucocorticoid-dependent REDD1 expression reduces muscle metabolism to enable adaptation under energetic stress

Cited by 35 publications

References 65 publications

Endurance exercise decreases protein synthesis and ER-mitochondria contacts in mouse skeletal muscle

Endurance exercise decreases protein synthesis and ER-mitochondria contacts in mouse skeletal muscle

Gut bacteria are critical for optimal muscle function: a potential link with glucose homeostasis

Assessment of fatigue-related biochemical alterations in a rat swimming model under hypoxia

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