Skeletal muscle is not only the largest energy metaboliser in the body, obesity effects directly on contractile function have been suggested to contribute to a negative obesity cycle. There is now a growing body of published work examining the effects of obesity on the contractile performance of skeletal muscle, and recent work using an isolated skeletal muscle model has been used to develop an understanding obesity effects directly at the muscle. Despite some ambiguity in findings, there is evidence to indicate that obesity will have a muscle and contractile modality specific effect on muscle function. The present thesis used an isolated skeletal muscle model to assess key gaps in the knowledge examining the effects of high fat diet (HFD) feeding duration on contractile function and assessing the influence of HFD on thermosensitivity of skeletal muscle. Furthermore, the present work uniquely examines the effect of HFD on eccentric muscle function, the interaction between muscle ageing and obesity and to what extent the effects of HFD can be reversed using calorie restriction and voluntary exercise. In order to establish muscle specific effects of the contractile function of isolated mouse soleus, extensor digitorum longus (EDL) and diaphragm are assed using isometric and work loop assessments. The work loop technique provides a more accurate evaluation of muscle function during dynamic muscle activity as per that used in vivo. Results from the present thesis are confirmatory of previous work indicating a contractile modality and muscle specific HFD effect, with evidence of an increase in absolute muscle performance in postural muscles and a reduction in muscle quality (muscle performance normalised to muscle size). These data provide an important novel contribution to our understanding of HFD effects on muscle by uniquely indicating HFD consumption may induce negative effects on eccentric function and do not follow the same patterns as the effects of concentric data, suggesting the mechanism which impact these changes may be different. Furthermore, these data indicate the importance of fat accumulation, rather than HFD duration is the most effective mediator of changes in muscle function. Here we demonstrate that a relatively short duration (8 weeks) of a HFD can induce negative effects on contractile function if high volumes of lipid accumulation occurs. Our results add clarity to ambiguous findings previously reported by indicating the effects of HFD on muscle function in the most part occur only around physiological temperatures, questioning the application of previous isolated muscle work examining HFD effects at lower temperatures, as well as reporting a HFD does not alter the thermosensitivity of skeletal muscles. Finally, these data uniquely indicate that long duration HFD consumption has limited effects on age related changes in muscle function, where a reduced calorie diet was beneficial for both morphology and contractility, whilst exercise gave greater contractility benefits but no such morphology changes.
|Date of Award||Feb 2020|
|Supervisor||Jason Tallis (Supervisor), Rob James (Supervisor) & Valerie Cox (Supervisor)|