PMID- 35417269 OWN - NLM STAT- MEDLINE DCOM- 20220517 LR - 20220616 IS - 1522-1563 (Electronic) IS - 0363-6143 (Linking) VI - 322 IP - 5 DP - 2022 May 1 TI - The regulating pathway of creatine on muscular protein metabolism depends on the energy state. PG - C1022-C1035 LID - 10.1152/ajpcell.00447.2021 [doi] AB - Creatine (Cr) is beneficial for increasing muscle mass and preventing muscle atrophy via involving in energy metabolism through the Cr and phosphocreatine (PCr) system. This study aimed to evaluate the supplemental effect of Cr on protein metabolism under normal and starvation conditions. The primary myoblasts were obtained from the breast muscle of chicks. The mammalian target of rapamycin (mTOR)/P70S6 kinase (P70S6K), ubiquitin-proteasome (UP) pathways, and mitochondrial function of myotubes were evaluated at normal or starvation state and with or without glucose supplementation. Under normal condition, Cr supplementation enhanced protein synthesis rate as well as upregulated the total and phosphorylated P70S6K expressions. Cr had little influence on protein catabolism and mitochondrial function. In a starvation state, however, Cr alleviated myotube atrophy and enhanced protein accretion by inhibiting Atrogin1 and myostatin (MSTN) expression. Furthermore, Cr treatment upregulated the transcriptional coactivators peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) expression and decreased reactive oxygen species (ROS) accumulation under starvation condition. In the presence of glucose, however, the favorable effect of Cr on protein content and myotube diameter did not occur under starvation condition. The present result indicates that at a normal state, Cr stimulated protein synthesis via the mTOR/P70S6K pathway. In a starvation state, Cr mainly takes a favorable effect on protein accumulation via suppression of the UP pathway and mediated mitochondrial function mainly by serving as an energy supplier. The result highlights the potential clinical application for the modulation of muscle mass under different nutritional conditions. FAU - Sun, Mingfa AU - Sun M AD - Department of Animal Science, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, People's Republic of China. FAU - Jiao, Hongchao AU - Jiao H AD - Department of Animal Science, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, People's Republic of China. FAU - Wang, Xiaojuan AU - Wang X AD - Department of Animal Science, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, People's Republic of China. FAU - Li, Haifang AU - Li H AD - College of Life Sciences, Shandong Agricultural University, Taian, People's Republic of China. FAU - Zhou, Yunlei AU - Zhou Y AD - College of Chemistry and Material Science, Shandong Agricultural University, Taian, People's Republic of China. FAU - Zhao, Jingpeng AU - Zhao J AD - Department of Animal Science, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, People's Republic of China. FAU - Lin, Hai AU - Lin H AUID- ORCID: 0000-0002-0878-137X AD - Department of Animal Science, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, People's Republic of China. LA - eng SI - figshare/10.6084/m9.figshare.19235691 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220413 PL - United States TA - Am J Physiol Cell Physiol JT - American journal of physiology. Cell physiology JID - 100901225 RN - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - IY9XDZ35W2 (Glucose) RN - MU72812GK0 (Creatine) SB - IM MH - Animals MH - Chickens MH - *Creatine/metabolism/therapeutic use MH - Energy Metabolism MH - Glucose/metabolism MH - Muscle, Skeletal/metabolism MH - Muscular Atrophy/metabolism MH - *Muscular Diseases/metabolism MH - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics/metabolism MH - Ribosomal Protein S6 Kinases, 70-kDa/metabolism MH - TOR Serine-Threonine Kinases/metabolism OTO - NOTNLM OT - creatine OT - glucose OT - mitochondrial quality OT - myotubes OT - protein metabolism EDAT- 2022/04/14 06:00 MHDA- 2022/05/18 06:00 CRDT- 2022/04/13 17:11 PHST- 2022/04/14 06:00 [pubmed] PHST- 2022/05/18 06:00 [medline] PHST- 2022/04/13 17:11 [entrez] AID - 10.1152/ajpcell.00447.2021 [doi] PST - ppublish SO - Am J Physiol Cell Physiol. 2022 May 1;322(5):C1022-C1035. doi: 10.1152/ajpcell.00447.2021. Epub 2022 Apr 13.