ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016
Skeletal muscle-specific eukaryotic translation initiation factor 2α phosphorylation controls amino acid metabolism and fibroblast growth factor 21-mediated non-cell-autonomous energy metabolism.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 61 citations in OpenAlex.
- Lifelong restriction of dietary valine has sex-specific benefits for health and lifespan in mice.Nature aging · 2026Article
- Unfolding Resilience: Molecular Integration of the Integrated Stress Response and Mitochondrial UPR in Skeletal Muscle Homeostasis.Muscles (Basel, Switzerland) · 2026Review
- Suppression rather than activation of the integrated stress response (GCN2-ATF4) pathway extends lifespan in the fly.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Selenoprotein N and SEPN1-Related Myopathies: Mechanisms, Models, and Therapeutic Perspectives.Biomolecules · 2026Review
- Signaling networks governing skeletal muscle growth, atrophy, and cachexiaSkeletal muscle · 2025Review
- Lifelong restriction of dietary valine has sex-specific benefits for health and lifespan in mice.bioRxiv : the preprint server for biology · 2025Article
- Homeostasis control in health and disease by the unfolded protein response.Nature reviews. Molecular cell biology · 2025Review
- Protective effects of Salubrinal against HFrontiers in pharmacology · 2025Article
- Article
- Induction of proteasomal activity in mammalian cells by lifespan-extending tRNA synthetase inhibitors.GeroScience · 2024Article
- FGF21 Induces Skeletal Muscle Atrophy and Increases Amino Acids in Female Mice: A Potential Role for Glucocorticoids.Endocrinology · 2024Article
- ATF4-dependent and independent mitokine secretion from OPA1 deficient skeletal muscle in mice is sexually dimorphic.Frontiers in endocrinology · 2024Article
- Critical variables regulating age-related anabolic responses to protein nutrition in skeletal muscle.Frontiers in nutrition · 2024Review
- Fibroblast Growth Factor 21: A Fascinating Perspective on the Regulation of Muscle Metabolism.International journal of molecular sciences · 2023Review
- Muscle-specific ER-associated degradation maintains postnatal muscle hypertrophy and systemic energy metabolism.JCI insight · 2023Article
- The transcription regulator ATF4 is a mediator of skeletal muscle aging.GeroScience · 2023Article
- A Label-Free Quantitative Analysis for the Search of Proteomic Differences between Goat Breeds.Animals : an open access journal from MDPI · 2022Article
- Circadian clock controls rhythms in ketogenesis by interfering with PPARα transcriptional network.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Biology of Activating Transcription Factor 4 (ATF4) and Its Role in Skeletal Muscle Atrophy.The Journal of nutrition · 2022Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
The eukaryotic translation initiation factor 2α (eIF2α) phosphorylation-dependent integrated stress response (ISR), a component of the unfolded protein response, has long been known to regulate intermediary metabolism, but the details are poorly worked out. We report that profiling of mRNAs of transgenic mice harboring a ligand-activated skeletal muscle-specific derivative of the eIF2α protein kinase R-like ER kinase revealed the expected up-regulation of genes involved in amino acid biosynthesis and transport but also uncovered the induced expression and secretion of a myokine, fibroblast growth factor 21 (FGF21), that stimulates energy consumption and prevents obesity. The link between the ISR and FGF21 expression was further reinforced by the identification of a small-molecule ISR activator that promoted Fgf21 expression in cell-based screens and by implication of the ISR-inducible activating transcription factor 4 in the process. Our findings establish that eIF2α phosphorylation regulates not only cell-autonomous proteostasis and amino acid metabolism, but also affects non-cell-autonomous metabolic regulation by induced expression of a potent myokine.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.