Investigation of muscle mass and metabolic regulation in human volunteers: the impact of resistance exercise, pharmacological intervention and obesity

Taylor, Tariq Yaqub (2020) Investigation of muscle mass and metabolic regulation in human volunteers: the impact of resistance exercise, pharmacological intervention and obesity. PhD thesis, University of Nottingham.

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Skeletal muscle is the most abundant tissue in the human body, yet is able to adapt to myriad exogenous or endogenous stimuli. Resistance exercise training is known to increase muscle cross-sectional area (CSA), muscle volume and strength. Optimisation of these adaptations is attempted via modalities that include variations in muscle contraction type, and pharmacological intervention. Conversely, in obesity, muscle protein synthetic response to anabolic stimuli is compromised, highlighting the need for interventions to minimise poor health outcomes and disability associated with impairments in muscle mass regulation.

The three experiments described in this thesis aimed to examine the effects of resistance exercise, pharmacological intervention and obesity on muscle mass and metabolic regulation. The first experimental chapter examined the temporal impact of 84 days of maximal combined concentric-eccentric versus maximal concentric training on muscular adaptations and targeted muscle mRNA expression in the young. Despite ~16% greater work done overall during concentric–eccentric training, no differences in muscle CSA, volume or strength were detected between modalities at any time during training. Gene networks linked to inflammation and regulation of myogenesis and muscle metabolism were altered in the initial week of training, but especially with concentric-eccentric training. However, these mRNA responses waned thereafter, regardless of modality. The second experimental chapter examined whether non-steroidal anti-inflammatory drug (NSAID) ingestion over 84 days of resistance training (i) increased training work output above placebo and (ii) impacted upon skeletal muscle adaptation by influencing the early inflammatory response observed in the young in the previous experimental chapter. Augmentation in muscle CSA and volume in the group consuming NSAIDs was found to be ~120% greater than placebo, occurring mainly from 28 days onward, paralleled by greater alteration in gene networks linked to myogenesis and muscle metabolic regulation. Strength did not increase in the NSAID group above placebo at any time during training, and training work output was similar between groups. The third experimental chapter examined whether forcibly increasing carbohydrate oxidation by oral dichloroacetate (DCA) administration might resolve the anabolic resistance in the elderly obese by increasing the efficiency of mitochondrial ATP production in a condition of lipid-induced muscle metabolic inflexibility. DCA administration increased myofibrillar fractional synthetic rate (FSR) in response to feeding ~40% above placebo. However, it did not increase myofibrillar FSR in response to combined feeding and exercise above placebo.

The resistance training studies in this thesis provided novel insight into the impact of eccentric exercise, and of NSAID administration on skeletal muscle adaptations. In combination with data from targeted gene network bioinformatics analysis, this added valuable knowledge on the impact of resistance exercise and medication on muscle mass regulation. Advances in the understanding of impaired anabolic response in the elderly obese were made by the novel experimental implementation of pharmacological intervention, while simultaneously opening up potential avenues in the management of conditions associated with muscle mass and metabolic dysregulation.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Greenhaff, Paul
Tsintzas, Kostas
Keywords: Muscle mass regulation, Resistance exercise, NSAIDs, Skeletal muscle adaptation, Carbohydrate oxidation, Dichloroacetate
Subjects: Q Science > QM Human anatomy
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Life Sciences
Item ID: 63484
Depositing User: Taylor, Tariq
Date Deposited: 11 Dec 2020 04:40
Last Modified: 11 Dec 2020 04:40

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