title: Glycine administration attenuates skeletal muscle wasting in a mouse model of cancer cachexia.
abstract: OBJECTIVE
  The non-essential amino acid, glycine, is often considered biologically neutral, but some studies indicate that it could be an effective anti-inflammatory agent. Since inflammation is central to the development of cancer cachexia, glycine supplementation represents a simple, safe and promising treatment. We tested the hypothesis that glycine supplementation reduces skeletal muscle inflammation and preserves muscle mass in tumor-bearing mice.
  
  
  METHODS
  To induce cachexia, CD2F1 mice received a subcutaneous injection of PBS (control, n = 12) or C26 tumor cells (n = 32) in accordance with the protocols developed by Murphy et al. [Murphy KT, Chee A, Trieu J, Naim T, Lynch GS. Importance of functional and metabolic impairments in the characterization of the C-26 murine model of cancer cachexia. Dis Models Mech 2012;5(4):533-545.]. Subcutaneous injections of glycine (n = 16) or PBS (n = 16) were administered daily for 21 days and at the conclusion of treatment, selected muscles, tumor and adipose tissue were collected and prepared for Real-Time RT-PCR or western blot analysis.
  
  
  RESULTS
  Glycine attenuated the loss of fat and muscle mass, blunted increases in markers of inflammation (F4/80, P = 0.01 & IL-6 mRNA, P = 0.01) and atrophic signaling (MuRF, P = 0.047; atrogin-1, P = 0.04; LC3B, P = 0.06 and; BNIP3, P = 0.10) and tended to attenuate the loss of body mass (P = 0.07), muscle function (P = 0.06), and oxidative stress (GSSG/GSH, P = 0.06 and DHE, P = 0.07) seen in tumor-bearing mice. Preliminary studies that compared the effect of glycine administration with isonitrogenous doses of alanine or citrulline showed that the observed protective effect was specific to glycine.
  
  
  CONCLUSIONS
  Glycine protects skeletal muscle from cancer-induced wasting and loss of function, reduces the oxidative and inflammatory burden, and reduces the expression of genes associated with muscle protein breakdown in cancer cachexia. Importantly, these effects were glycine specific.
authors.affiliation: Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Victoria 3010, Australia.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Ham
authors.affiliation: Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Victoria 3010, Australia.
authors.forename: Kate T
authors.initials: KT
authors.lastname: Murphy
authors.affiliation: Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Victoria 3010, Australia.
authors.forename: Annabel
authors.initials: A
authors.lastname: Chee
authors.affiliation: Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Victoria 3010, Australia.
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Lynch
authors.affiliation: Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Victoria 3010, Australia. Electronic address: rkoopman@unimelb.edu.au.
authors.forename: René
authors.initials: R
authors.lastname: Koopman
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015992:Body Mass Index; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005998:Glycine / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy*; D007371:Interferon-gamma / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D009133:Muscular Atrophy; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D005230:Fatty Acids, Nonesterified; D053583:Interleukin-1beta; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D005998:Glycine
keywords: C-26 tumor-bearing mice; Inflammation; Muscle function; Muscle mass