title: Alpha-ketoglutarate promotes skeletal muscle hypertrophy and protein synthesis through Akt/mTOR signaling pathways.
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.
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
authors.forename: Xingcai
authors.initials: X
authors.lastname: Cai
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
authors.forename: Canjun
authors.initials: C
authors.lastname: Zhu
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Jing
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
authors.forename: Yexian
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
authors.forename: Songbo
authors.initials: S
authors.lastname: Wang
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gao
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, 510642, China.|ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou 510642, PR China.
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, 510642, China.|ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou 510642, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Shu
mesh_terms: D000818:Animals; D002460:Cell Line; D055785:Gene Knockdown Techniques; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006984:Hypertrophy / Q000139:chemically induced / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000494:pharmacology* / Q000633:toxicity; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000648:ultrastructure; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*
chemical_list: C531499:GPR91 protein, mouse; D007656:Ketoglutaric Acids; D009124:Muscle Proteins; C486887:OXGR1 protein, mouse; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D018048:Receptors, Purinergic P2; D018698:Glutamic Acid; C546843:mTOR protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases