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Patterns of gene expression in atrophying skeletal muscles: response to food deprivation
Abstract
During fasting and many systemic diseases, muscle undergoes rapid loss of protein and functional capacity. To define the transcriptional changes triggering muscle atrophy and energy conservation in fasting, we used cDNA microarrays to compare mRNAs from muscles of control and food‐deprived mice. Expression of >94% of genes did not change, but interesting patterns emerged among genes that were differentially expressed: 1) mRNAs encoding polyubiquitin, ubiquitin extension proteins, and many (but not all) proteasome subunits increased, which presumably contributes to accelerated protein breakdown; 2) a dramatic increase in mRNA for the ubiquitin ligase, atrogin‐1, but not most E3s; 3) a significant suppression of mRNA for myosin binding protein H (but not other myofibrillar proteins) and IGF binding protein 5, which may favor cell protein loss; 4) decreases in mRNAs for several glycolytic enzymes and phosphorylase kinase subunits, and dramatic increases in mRNAs for pyruvate dehydrogenase kinase 4 and glutamine synthase, which should promote glucose sparing and gluconeogenesis. During fasting, metallothionein mRNA increased dramatically, mRNAs for extracellular matrix components fell, and mRNAs that may favor cap‐independent mRNA translation rose. Significant changes occurred in mRNAs for many growth‐related proteins and transcriptional regulators. These transcriptional changes indicate a complex adaptive program that should favor protein degradation and suppress glucose oxidation in muscle. Similar analysis of muscles atrophying for other causes is allowing us to identify a set of atrophy‐specific changes in gene expression.—Jagoe, R. T., Lecker, S. H., Gomes, M., Goldberg, A. L. Patterns of gene expression in atrophying skeletal muscles: response to food deprivation. FASEB J . 16, 1697–1712 (2002)
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“Surprisingly, fasting produces changes in gene expression that are strikingly similar to the pattern of fat-induced changes observed in our studies of HFDs.”
From A High-Fat Diet Coordinately Downregulates Genes Required for Mitochondrial Oxidative Phosphorylation in Skeletal Muscle (2005) · cites this paper as Jagoe et al. (37)
In the citing paper
“Jagoe et al. (37) found that CASQ2 (calsequestrin 2), NDUFS1, glycogen synthase, and pyruvate dehydrogenase kinase isoenzyme 4, four genes found on our microarray”
From A High-Fat Diet Coordinately Downregulates Genes Required for Mitochondrial Oxidative Phosphorylation in Skeletal Muscle (2005) · cites this paper as Jagoe et al. (37)
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Self-citation
Metadata
- Authors
- Jagoe, R. T., Lecker, S. H., Gomes, M., & Goldberg, A. L.
- Affiliations
- Harvard University (US)
- Beth Israel Deaconess Medical Center (US)
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2002-11
- Volume
- 16
- Issue
- 13
- Pages
- 1697-1712
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2101050876
- Cited by
- 344
- References
- 102
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 7 · 2023: 4 · 2022: 7 · 2021: 8 · 2020: 7 · 2019: 13 · 2018: 10 · 2017: 14 · 2016: 12 · 2015: 16 · 2014: 10 · 2013: 13 · 2012: 28
- FWCI
- 7.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Space Biomedical Research Institute
- National Institutes of Health (DK02707)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
- Keywords
- skeletal muscle atrophy, fasting, food deprivation, gene expression, protein degradation, ubiquitin-proteasome system, atrogin-1, IGF binding protein-5, glycolytic enzymes, PDK4, glutamine synthetase, gluconeogenesis, glucose sparing, metallothionein, extracellular matrix, cap-independent translation, transcriptional regulation
- MeSH terms
- Animals, Atrophy, Body Weight, Cell Division, Creatine Kinase, Electron Transport, Food Deprivation, Gene Expression Regulation, Glutamate-Ammonia Ligase, Glycolysis, Male, Mice, Inbred C57BL, Endopeptidases, RNA, Messenger, Transcription Factors, Apoptosis, Muscle, Skeletal, Insulin-Like Growth Factor Binding Protein 5, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Carbonic Anhydrase III, Mice
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