Investigating the relationship between skeletal muscle inflammation, protein synthesis and mass in humans, using eccentric exercise, limb immobilisation, critical care, and resistance training models.
Jameson, T
Date: 24 May 2021
Thesis or dissertation
Publisher
University of Exeter
Degree Title
Doctor of Philosophy in Sport and Health Sciences
Abstract
Inflammation and muscle protein turnover are necessary processes that underpin the plasticity, mass and function of skeletal muscle during health and disease. The principle aim of this thesis was to test the hypothesis that inflammation regulates myofibrillar protein synthesis rates to determine changes in muscle function and mass in ...
Inflammation and muscle protein turnover are necessary processes that underpin the plasticity, mass and function of skeletal muscle during health and disease. The principle aim of this thesis was to test the hypothesis that inflammation regulates myofibrillar protein synthesis rates to determine changes in muscle function and mass in healthy and critically ill humans. Firstly, a nutrition intervention approach was used to investigate the time course of free-living myofibrillar protein synthesis rates and transcriptional inflammatory NF-κB and proteolytic signalling with respect to the recovery of muscle function after muscle-damaging eccentric contractions. Eccentric contractions were then combined with a unilateral limb immobilisation model to investigate the regulation of myofibrillar protein synthesis rates, muscle atrophy and muscle function by inflammation under disuse conditions. Using critically ill patients as a model of pathophysiological inflammation and muscle protein turnover, the effect of an exercise intervention administered in the intensive care unit on gene expression associated with inflammation and protein turnover was then investigated with respect to prospective functional outcomes in survivors. Finally, this thesis aimed to determine if early gains in muscle function in response to an eccentric biased resistance exercise training programme can be expedited nutritionally. The studies presented in this thesis demonstrate for the first time that an increase in myofibrillar protein synthesis rates are likely to be directly related to the decline in muscle function after myofibrillar injury. A primary novel finding of this thesis is that using nutrition or immobilisation to manipulate muscle function occurs independently of changes in myofibrillar protein synthesis rates. Additionally, this thesis presents novel data to show that inflammatory NF-κB signalling does not regulate myofibrillar proteins synthesis rates in healthy individuals and likely does not regulate changes in muscle function. We present preliminary data suggesting that muscle protein breakdown may instead be important. A final novel and pertinent conclusion of this thesis is that pathophysiological inflammation in the critically ill patient is associated with failed skeletal muscle remodelling in response to muscle contraction, and this is associated with poor functional outcomes in survivors. These findings could be of major relevance for athletic, general and clinical populations where muscle mass and function underpin athletic performance, quality of life and life itself.
Doctoral Theses
Doctoral College
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