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Impact of ghrelin on body composition and muscle function in a long-term rodent model of critical illness

Hill, NE; Murphy, KG; Saeed, S; Phadke, R; Chambers, D; Wilson, DR; Brett, SJ; (2017) Impact of ghrelin on body composition and muscle function in a long-term rodent model of critical illness. PLoS ONE , 12 (8) , Article e0182659. 10.1371/journal.pone.0182659. Green open access

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Abstract

BACKGROUND: Patients with multiple injuries or sepsis requiring intensive care treatment invariably develop a catabolic state with resultant loss of lean body mass, for which there are currently no effective treatments. Recovery can take months and mortality is high. We hypothesise that treatment with the orexigenic and anti-inflammatory gastric hormone, ghrelin may attenuate the loss of body mass following critical illness and improve recovery. METHODS: Male Wistar rats received an intraperitoneal injection of the fungal cell wall derivative zymosan to induce a prolonged peritonitis and consequent critical illness. Commencing at 48h after zymosan, animals were randomised to receive a continuous infusion of ghrelin or vehicle control using a pre-implanted subcutaneous osmotic mini-pump, and continued for 10 days. RESULTS: Zymosan peritonitis induced significant weight loss and reduced food intake with a nadir at Day 2 and gradual recovery thereafter. Supra-physiologic plasma ghrelin levels were achieved in the treated animals. Ghrelin-treated rats ate more food and gained more body mass than controls. Ghrelin increased adiposity and promoted carbohydrate over fat metabolism, but did not alter total body protein, muscle strength nor muscle morphology. Muscle mass and strength remained significantly reduced in all zymosan-treated animals, even at ten days post-insult. CONCLUSIONS: Continuous infusion of ghrelin increased body mass and food intake, but did not increase muscle mass nor improve muscle function, in a long-term critical illness recovery model. Further studies with pulsatile ghrelin delivery or additional anabolic stimuli may further clarify the utility of ghrelin in survivors of critical illness.

Type: Article
Title: Impact of ghrelin on body composition and muscle function in a long-term rodent model of critical illness
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0182659
Publisher version: http://dx.doi.org/10.1371/journal.pone.0182659
Language: English
Additional information: © 2017 Hill et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, PLACEBO-CONTROLLED TRIAL, FOOD-INTAKE, THERMAL-INJURY, HEART-FAILURE, ILL ADULTS, RAT MODEL, CACHEXIA, NUTRITION, SEPSIS, METABOLISM
URI: http://discovery.ucl.ac.uk/id/eprint/10043215
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