Cited by 54Muscle metabolism and nutritionMuscle Physiology and DisordersMetabolism, Diabetes, and Cancer

RETRACTED ARTICLE: Alpha-ketoglutarate promotes skeletal muscle hypertrophy and protein synthesis through Akt/mTOR signaling pathways

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Cai, Xingcai, Zhu, Canjun, Xu, Yaqiong, Jing, Yuanyuan, Yuan, Yexian, Wang, Lina, Wang, Songbo, Zhu, Xiaotong +4 more·2016·Scientific Reports

Abstract

Skeletal muscle weight loss is accompanied by small fiber size and low protein content. Alpha-ketoglutarate (AKG) participates in protein and nitrogen metabolism. The effect of AKG on skeletal muscle hypertrophy has not yet been tested, and its underlying mechanism is yet to be determined. In this study, we demonstrated that AKG (2%) increased the gastrocnemius muscle weight and fiber diameter in mice. Our in vitro study also confirmed that AKG dose increased protein synthesis in C2C12 myotubes, which could be effectively blocked by the antagonists of Akt and mTOR. The effects of AKG on skeletal muscle protein synthesis were independent of glutamate, its metabolite. We tested the expression of GPR91 and GPR99. The result demonstrated that C2C12 cells expressed GPR91, which could be upregulated by AKG. GPR91 knockdown abolished the effect of AKG on protein synthesis but failed to inhibit protein degradation. These findings demonstrated that AKG promoted skeletal muscle hypertrophy via Akt/mTOR signaling pathway. In addition, GPR91 might be partially attributed to AKG-induced skeletal muscle protein synthesis.

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  1. You J. S., Anderson G. B., Dooley M. S.& Hornberger T. A. The role of mTOR signaling in the regulation of protein synthesis and muscle mass during immobilization. Dis Model Mech 8, 1059– 1069 (2015). 26092121 PMC4582099

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Authors
Cai, X., Zhu, C., Xu, Y., Jing, Y., Yuan, Y., Wang, L., Wang, S., Zhu, X., Gao, P., Zhang, Y., Jiang, Q., & Shu, G.
Affiliations
South China Agricultural University (CN)
Corresponding author
  • Jiang, Qingyan
  • Shu, Gang
Venue
Scientific Reports
Published
2016-05-26
Volume
6
Issue
1
Pages
26802-26802
ISSN
2045-2322 (ISSN-L)
OpenAlex
W2405506616
Cited by
54
References
56
Citations by year
2024: 3 · 2023: 4 · 2022: 6 · 2021: 5 · 2020: 11 · 2019: 11 · 2018: 3 · 2017: 9 · 2016: 2
FWCI
5.74
Type
journal article
Language
en
Status
Retracted
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Key Research and Development Program of China (2012CB124701, 2013CB127306)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
alpha-ketoglutarate, skeletal muscle hypertrophy, muscle protein synthesis, Akt/mTOR signaling, GPR91, gastrocnemius, muscle fiber diameter, C2C12 myotubes, protein degradation, glutamate metabolism
MeSH terms
Animals, Cell Line, Hypertrophy, Ketoglutaric Acids, Mice, Inbred C57BL, Muscle Proteins, Phosphorylation, Protein Processing, Post-Translational, Signal Transduction, Receptors, Purinergic P2, Muscle, Skeletal, Muscle Fibers, Skeletal, Glutamic Acid, RNA Interference, RNA, Small Interfering, Receptors, G-Protein-Coupled, Proto-Oncogene Proteins c-akt, Gene Knockdown Techniques, TOR Serine-Threonine Kinases

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