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The Importance of Intramuscular Triglyceride Turnover on Skeletal Muscle Insulin Sensitvity

Barrett, J (2023) The Importance of Intramuscular Triglyceride Turnover on Skeletal Muscle Insulin Sensitvity. Doctoral thesis, Liverpool John Moores University.

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High intramuscular triglyceride (IMTG) stores in sedentary, obese and elderly individuals have been linked to insulin resistance, yet elite athletes often have higher amounts of IMTG whilst maintaining a high muscle and whole-body insulin sensitivity. It is now known that a high IMTG content per se does not result in insulin resistance, but is caused, at least in part, by the presence of high muscle concentrations of harmful lipid metabolites, such as diacylglycerols (DAGs) and ceramides. The latter are elevated in obesity and type 2 diabetes (T2D) (Goodpaster et al., 1997; Pan et al., 1997; Forouhi et al., 1999) in comparison to healthy lean controls. Individuals with T2D demonstrate reduced IMTG turnover rates compared to those that are insulin sensitive and/or well trained. This thesis focuses first on the adaptations that affect IMTG turnover and explores methods in which IMTG utilisation can be targeted in obese individuals to reduce the risk of developing T2D, specifically focussing on the ingestion of an antilipolytic drug combined with exercise, as well as fasted exercise training. Chapter 4 determined that following exposure to high plasma free fatty acids (FFA), GLUT4 translocation to the plasma membrane is unaltered in both trained and sedentary individuals. Interestingly, we report that in both trained and sedentary individuals GLUT4 expression is higher in both type 1 and type 2 fibres in trained individuals, who have more small GLUT4 spots making up ~97% of total GLUT4 spots. Chapter 5 demonstrated that exercising with reduced plasma FFA via lipolytic inhibition leads to reduced ceramide 20:0 accumulation and an increase in several lactosylceramide species. Chapter 6 demonstrated that targeting IMTG turnover in a 12-week home-based walking programme by exercising in the fasted state (known to lead to greater IMTG utilisation) compared to the fed state made little difference to the effectiveness of the intervention to improve glucose tolerance and reduce HbA1c (~7% FAST, ~2% FED). However, exercising in the fasted state during the programme also reduced alanine transferase concentrations compared to fed state exercise (~16% FAST, ~2% FED). In conclusion, this thesis presents novel data on the differences in insulin signalling in both trained and sedentary individuals. Furthermore, data is presented on the health benefits resulting from interventions in obese individuals that target the use of IMTG stores during exercise, and therefore, result in greater turnover of IMTG stores.

Item Type: Thesis (Doctoral)
Uncontrolled Keywords: Insulin Sensitivity; Exercise; Intramuscular Triglyceride
Subjects: R Medicine > RC Internal medicine > RC1200 Sports Medicine
Divisions: Sport & Exercise Sciences
SWORD Depositor: A Symplectic
Date Deposited: 09 Feb 2023 12:25
Last Modified: 09 Feb 2024 00:50
DOI or ID number: 10.24377/LJMU.t.00018786
Supervisors: Shepherd, S, Strauss, J, Wagenmakers, A and Cuthbertson, D
URI: https://researchonline.ljmu.ac.uk/id/eprint/18786
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