Protective Effects of Glutamine and Leucine Supplementation on Sepsis-Induced Skeletal Muscle Injuries

• Published in: International journal of molecular sciences Vol. 22; no. 23; p. 13003
• Main Authors: Hou, Yu-Chen, Pai, Man-Hui, Wu, Jin-Ming, Yang, Po-Jen, Lee, Po-Chu, Chen, Kuen-Yuan, Yeh, Sung-Ling, Lin, Ming-Tsan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.11.2021; MDPI
• Subjects: Amino acids; Animals; Anti-Inflammatory Agents - therapeutic use; Biomolecules; Biosynthesis; Blood; Calpain; Calpain - metabolism; Cecum; Cytokines; Cytokines - biosynthesis; Gene expression; Glutamine; Glutamine - therapeutic use; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - biosynthesis; hypoxia-inducible factor-1α; Hypoxia-inducible factors; Inflammation; Inflammation - prevention & control; Injuries; Leucine; Leucine - therapeutic use; Leukocytes; Lipid peroxidation; macrophage; Macrophages; Macrophages - physiology; Male; Metabolism; Mice; Mice, Inbred C57BL; mitochondria; monocyte; Monocytes; Monocytes - physiology; Mortality; Muscle, Skeletal - injuries; Muscle, Skeletal - pathology; Muscles; Musculoskeletal system; Neutrophils; Oxidative Stress - drug effects; Phenotypes; Protein synthesis; Proteins; Sepsis; Sepsis - pathology; Skeletal muscle; Surgery; Synergistic effect; Tumor necrosis factor-TNF; calpain; macrophage; monocyte; hypoxia-inducible factor-1α; mitochondria
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222313003

This study investigated the effects of l-glutamine (Gln) and/or l-leucine (Leu) administration on sepsis-induced skeletal muscle injuries. C57BL/6J mice were subjected to cecal ligation and puncture to induce polymicrobial sepsis and then given an intraperitoneal injection of Gln, Leu, or Gln plus Leu beginning at 1 h after the operation with re-injections every 24 h. All mice were sacrificed on either day 1 or day 4 after the operation. Blood and muscles were collected for analysis of inflammation and oxidative damage-related biomolecules. Results indicated that both Gln and Leu supplementation alleviated sepsis-induced skeletal muscle damage by reducing monocyte infiltration, calpain activity, and mRNA expression levels of inflammatory cytokines and hypoxia-inducible factor-1α. Furthermore, septic mice treated with Gln had higher percentages of blood anti-inflammatory monocytes and muscle M2 macrophages, whereas Leu treatment enhanced the muscle expressions of mitochondrion-related genes. However, there were no synergistic effects when Gln and Leu were simultaneously administered. These findings suggest that both Gln and Leu had prominent abilities to attenuate inflammation and degradation of skeletal muscles in the early and/or late phases of sepsis. Moreover, Gln promoted the switch of leukocytes toward an anti-inflammatory phenotype, while Leu treatment maintained muscle bioenergetic function.