The Effects of Obesity on Skeletal Muscle Health

: An Investigation of Contractile Performance and Nutritional Therapeutic Strategies

Abstract

Obesity has previously shown to be detrimental to skeletal muscle contractile function, which may exacerbate the adverse health effects and comorbidities associated with obesity. Despite the damaging effects of obesity on skeletal muscle health, not all aspects of skeletal muscle contractility have been thoroughly considered. Understanding obesity effects on contractile function across a range of contractile modes and muscles is needed for a holistic understanding of how obesity effects muscle performance, which helps inform potential strategies to offset negative obesity effects. Furthermore, current non-surgical treatment strategies to reduce the impact of obesity on skeletal muscle performance have poor adherence and long-term success rates, thus alternative appealing strategies should be considered. Using a combination of human in vivo and rodent isolated skeletal muscle models, the present thesis examines: the contractile mode and muscle specific effects of obesity on skeletal muscle contractile function; the concomitant effects of obesity and aging on skeletal muscle contractility; potential nutritional strategies to offset the adverse effects of obesity on skeletal muscle function. Furthermore, the present work further refines the protocols used to examine isolated skeletal muscle contractile performance, appeasing some of the concerns regarding in vivo replicability of fatigue measures obtained from the work loop model. The current thesis is the first to report the effects of obesity on eccentric muscle performance, and uniquely identifies the simultaneous effects of obesity and aging on contractile performance, using isokinetic dynamometry, the gold standard for strength assessments in vivo. Isolated skeletal muscle models were used to determine the effects of high fat diet (HFD), vitamin D, and resveratrol consumption on isolated muscle contractile properties, where the focus was on the work loop (WL) model. The WL model better replicates the dynamic nature of in vivo skeletal muscle mechanics compared to most in vitro assessments of contractile function of skeletal muscle. Experimental study 1, for the first time, identifies that obesity adversely effects eccentric muscle performance in a contractile mode and muscle specific manner, which is not entirely concurrent with changes in concentric function. Furthermore, the study identifies that obesity induced changes in muscle function are not exacerbated by aging, but are likely more substantial in older adults due to the age-related decline in muscle function. Experimental study 2 uniquely establishes that the stimulation frequency needed to evoke maximal power output in isolated mouse EDL exceeds that needed for maximal isometric force, and that submaximal stimulation frequency is needed to evoke a fatigue response representative of in vivo fatigue mechanics. Using the refined WL protocol established in experimental study 2, experimental study 3 and 4 identify that HFD effects on isolated skeletal muscle function are contractile mode and muscle specific, but appear more substantial in fast twitch muscle. For the first time the present thesis identifies that HFD evokes a reduction in cumulative work production in both fast twitch EDL and slow twitch soleus during fatiguing contractions, but does not influence rate of fatigue relative to maximum power output. Experimental study 3 provides the first evidence to suggest that a high dose of vitamin D does not attenuate the reduction in contractile performance associated with HFD feeding. Experimental study 4 uniquely establishes that resveratrol reduces the impact of HFD feeding on acute and sustained power production of isolated mouse EDL. As such, this thesis provides the first direct evidence to suggest resveratrol may be an effective nutritional strategy to reduce the impact of obesity on isolated skeletal muscle function.

Date of Award	Sept 2022
Original language	English
Awarding Institution	Coventry University
Supervisor	Jason Tallis (Supervisor), Rob James (Supervisor), Steven Eustace (Supervisor) & Emma Eyre (Supervisor)