Marginal dietary zinc deprivation augments sepsis-induced alterations in skeletal muscle TNF-α but not protein synthesis.
Severe zinc deficiency is associated with an increased systemic inflammatory response and mortality after sepsis. However, the impact of mild zinc deficiency, which is more common in populations with chronic illnesses and sepsis, is unknown. In this study, we hypothesized that marginal dietary Zn deprivation (ZM) would amplify tissue inflammation and exacerbate the sepsis-induced decrease in muscle protein synthesis. Adult male C57BL/6 mice were fed a zinc-adequate (ZA) or ZM diet (30 or 10 mg Zn/kg, respectively) over 4 weeks, peritonitis was induced by cecal ligation and puncture (CLP), and mice were examined at either 24 h (acute) or 5 days (chronic) post-CLP Acute sepsis decreased the in vivo rate of skeletal muscle protein synthesis and the phosphorylation of the mTOR substrate 4E-BP1. Acutely, sepsis increased TNF-α and IL-6 mRNA in muscle, and the increase in TNF-α was significantly greater in ZM mice. However, muscle protein synthesis and 4E-BP1 phosphorylation returned to baseline 5 days post-CLP in both ZA and ZM mice. Protein degradation via markers of the ubiquitin proteasome pathway was increased in acute sepsis, yet only MuRF1 mRNA was increased in chronic sepsis and ZM amplified this elevation. Our data suggest that mild zinc deficiency increases TNF-α in muscle acutely after sepsis but does not significantly modulate the rate of muscle protein synthesis.
Department of Surgery, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania.
Kristen T
KT
Crowell
Department of Surgery, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania.|Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania.|Department of Pharmacology, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania.|Department of Nutritional Sciences, Pennsylvania State University, University Park, Pennsylvania.
Shannon L
SL
Kelleher
Department of Surgery, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania.|Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania.|Department of Nutritional Sciences, Pennsylvania State University, University Park, Pennsylvania.
David I
DI
Soybel
Department of Surgery, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania clang@hmc.psu.edu.|Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania.
Charles H
CH
Lang
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000378:metabolism*; D010538:Peritonitis / Q000378:metabolism / Q000503:physiopathology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D018805:Sepsis / Q000378:metabolism* / Q000503:physiopathology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D000070584:Tripartite Motif Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D019282:Wasting Syndrome / Q000378:metabolism*; D015032:Zinc / Q000172:deficiency* / Q000378:metabolism / Q000494:pharmacology
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D015850:Interleukin-6; D009124:Muscle Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D000070584:Tripartite Motif Proteins; D014409:Tumor Necrosis Factor-alpha; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D015032:Zinc
Inflammation; muscle wasting; sepsis; skeletal muscle metabolism; zinc deficiency