Investigating the effects of low protein diet on the neuromuscular system


Ersoy, Ufuk (2024) Investigating the effects of low protein diet on the neuromuscular system. PhD thesis, University of Liverpool.

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Abstract

The nutritional environment encountered during early life can impact the risk of developing age-related diseases such as sarcopenia. As a highly dynamic tissue, skeletal muscle is particularly vulnerable to nutritional deficiencies during its development compared to other tissues, highlighting the importance of an optimal maternal diet for skeletal muscle development. Dysregulated myogenesis, a reduction in muscle fibre numbers, changes in the distribution of fibre type, alterations in skeletal muscle mass and metabolism, as well as changes in the expression levels of key mitochondrial genes, have been observed in the skeletal muscles of offspring nursed by dams on an isocaloric low-protein diet. However, the long-term effects of protein restriction during lactation on skeletal muscle remain unknown. The aims of this thesis were to 1) investigate the effects of lactational protein restriction on skeletal muscle and to establish whether early adverse effects persist following weaning onto a normal protein diet later in life; 2) to examine the impact of feeding a lifelong low-protein diet on the neuromuscular system in murine offspring during ageing. The main findings of this thesis are: • Lactational protein restriction resulted in a muscle specific growth restriction in mice, and this was associated with changes in the expression level of genes involved in ribosomal homeostasis, mitochondrial adenosine triphosphate (ATP) synthesis regulation, the transition between fast and slow muscle fibre, muscle structure development, skeletal muscle fibre development, and membrane organisation. • Lifelong protein restriction led to a decrease in muscle fibre size and accelerated skeletal muscle loss, which correlated with impaired AMP-activated protein kinase (AMPK) signalling, dysregulated mitochondrial homeostasis, and proteostasis. • Lifelong protein restriction induced skeletal muscle atrophy through impairments in proteostasis at the molecular level, potentially driven by denervation-induced changes. • Switching to a normal protein diet after weaning can reverse the detrimental effects of lactational protein restriction on the neuromuscular system later in life. In conclusion, this thesis provided novel insight into the mechanisms by which lactational protein restriction impaired skeletal muscle growth and presented evidence that lifelong dietary protein restriction induced detrimental effects on the neuromuscular system in later life. Translation of these findings to human health could potentially revolutionise the guidelines for an optimal maternal nutritional diet.

Item Type: Thesis (PhD)
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 19 Aug 2025 15:33
Last Modified: 19 Aug 2025 15:33
DOI: 10.17638/03189030
Supervisors:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3189030
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