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

Yu-Chen Hou,Man-Hui Pai,Kuen-Yuan Chen,Po-Jen Yang,Po-Chu Lee,Jin-Ming Wu,Sung-Ling Yeh,Ming-Tsan Lin

doi:10.3390/ijms222313003

Abstract

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.

Highlights

Sepsis is systemic inflammation induced by severe infection that commonly occurs in critically ill patients
Thegroups groupsare aredescribed described in in the the legend legend to Intensive care unit (ICU)-acquired weakness is a major cause of long-term morbidity andIntensive mortalitycare in critically ill patients, andweakness sepsis survivors havecause higher of developing unit (ICU)-acquired is a major ofrisk long-term morbidity myopathies that worsen disease outcomes
We found that compared to the C group, percentages of blood neutrophils, macrophages, and inflammatory monocytes were elevated in the sepsis groups; neutrophil and monocyte infiltration and a higher M1/M2 macrophage ratio were observed in skeletal muscles of septic mice

Summary

Introduction

Sepsis is systemic inflammation induced by severe infection that commonly occurs in critically ill patients. Prolonged weakness is a major cause of morbidity and mortality in this critical illness [1,2], and sepsis is a major risk factor for acquired muscle weakness [3,4]. Excessive localized elaboration of proinflammatory cytokines, free-radical generation, activation of proteolytic pathways, and altered mitochondrial bioenergetic function play critical roles in sepsisassociated myopathic changes [6]. Inhibition of these pathways may attenuate muscle injuries and prevent the progression of sepsis-induced myopathies

Methods

Discussion

Conclusion