Nutritional regulation of mitochondrial biogenic energy-sensing pathways in skeletal muscle following endurance exercise

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Stocks, Ben (2019). Nutritional regulation of mitochondrial biogenic energy-sensing pathways in skeletal muscle following endurance exercise. University of Birmingham. Ph.D.

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Abstract

Endurance exercise improves health partly though improvements in skeletal muscle function. Mitochondrial biogenesis is one of the mechanisms that underpin the positive health benefits of endurance exercise. Endurance-exercise and energy sensitive pathways signal to promote transcriptional processes that initiate the adaptive response. Thus the aim of this thesis was to further understand the regulation of post-exercise signalling within skeletal muscle, with specific focus on the activation of energy-sensitive mitochondrial biogenic signalling pathways. It was demonstrated that muscle-specific knockout of p53 does not impair mitochondrial protein content or enzyme activity within mouse skeletal muscle. In human skeletal muscle, fasting and fasted-exercise augment CREB\(^S\)\(^e\)\(^r\)\(^1\)\(^3\)\(^3\) and AMPK\(^T\)\(^h\)\(^r\)\(^1\)\(^7\)\(^2\) phosphorylation, while the mRNA expression of \(PDK4\) but not \(PPARGC1A\) is also increased in the fasted state. Finally, one week of nicotinamide riboside supplementation did not alter skeletal muscle mitochondrial respiration and whole-body substrate utilisation at rest or during endurance exercise, while SIRT1 and 3 activity and \(PPARGC1A\) mRNA expression at rest and following endurance-exercise are also unaffected by nicotinamide riboside supplementation. Overall, this thesis contributes novel data to the understanding of metabolism and skeletal muscle signalling following endurance exercise and how nutrition and endurance exercise could be integrated to optimise specific adaptations.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):