Cited by 149Muscle Physiology and DisordersMuscle metabolism and nutritionNutrition and Health in Aging

Signaling pathways weigh in on decisions to make or break skeletal muscle

Guttridge, Denis C·2004·Current Opinion in Clinical Nutrition and Metabolic Care

Abstract

PURPOSE OF REVIEW: Regulation of muscle size is essential for proper development and homeostasis of adult musculature. This regulation is mediated in large part by signal transduction pathways that promote the synthesis or breakdown of skeletal muscle. PI(3)K/Akt, myostatin and NF-kappaB represent three such pathways that will be the focus of this review. RECENT FINDINGS: Recent reports solidify the requirement of the PI(3)K/Akt pathway in the regulation of muscle hypertrophy. In response to IGF-1, Akt activates downstream effectors, mTOR and p70S6K to stimulate protein synthesis thereby increasing the cytoplasmic compartment in muscle fibers. Tsc2 was also identified as a novel Akt target, whose phosphorylation and inactivation by Akt may lead to an increase in cell size. The mechanisms by which myostatin functions in muscle wasting was recently explored using in-vitro assays of myogenesis. Myostatin was found to repress myogenesis by inhibiting the synthesis and activity of MyoD. Paradoxically, myostatin expression is itself regulated by MyoD binding to the myostatin promoter. The NF-kappaB transcription factor also functions as a negative regulator of myogenesis by inhibiting MyoD. Chronic activation of NF-kappaB has been associated with muscle wasting, but the mechanisms by which this regulation occurs remain for the most part unknown. SUMMARY: Recent cell culture and animal studies have provided insight on the mechanisms by which Akt, myostatin, and NF-kappaB signaling pathways regulate muscle size. Clinical intervention to boost Akt signaling or modulate myostatin and NF-kappaB activities may prove useful in diseases associated with chronic muscle wasting.

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Crossref · 10.1097/01.mco.0000134364.61406.26

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Authors
Guttridge, D. C.
Venue
Current Opinion in Clinical Nutrition and Metabolic Care
Published
2004-07
Volume
7
Issue
4
Pages
443-450
ISSN
1363-1950 (ISSN-L)
OpenAlex
W1990872004
Cited by
149
References
70
Citations by year
2026: 1 · 2024: 1 · 2023: 2 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 5 · 2017: 1 · 2016: 4 · 2015: 8 · 2014: 7 · 2013: 13 · 2012: 7
FWCI
1.14
Type
journal article
Language
en
Open access
closed
Locations
  • Current Opinion in Clinical Nutrition & Metabolic Care (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
Keywords
muscle hypertrophy, muscle atrophy, PI3K/Akt signaling, myostatin, NF-κB, insulin-like growth factor I, mTOR, p70S6K, TSC2, MyoD, myogenesis, protein synthesis
MeSH terms
Animals, Humans, Muscular Atrophy, Protein Kinases, Proto-Oncogene Proteins, Somatomedins, Signal Transduction, Transforming Growth Factor beta, NF-kappa B, Protein Serine-Threonine Kinases, Muscle, Skeletal, Proto-Oncogene Proteins c-akt, Myostatin, TOR Serine-Threonine Kinases

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