The global epidemic of obesity is rapidly becoming a major public health problem in many parts of the world. Unhealthy diets and physical inactivity are two modifiable risk factors for prevention of obesity and its associated chronic diseases. Their influence on muscle energy metabolism and fat mass is not completely elucidated. A decreased capacity for fatty acid oxidation (FAO) may be a metabolic risk factor for weight gain and is found to be depressed in obese individuals; and exercise training may promote an increased capacity for FAO. In addition to the interest in whole-body FAO, the role of site specific lipid accumulation including visceral adipose tissue (VAT), intrahepatic lipids (IHL) and intramyocellular lipids (IMCL) has become a focus of interest because of their reported association with insulin resistance (IR), a key metabolic defect associated with obesity and type 2 diabetes mellitus (T2DM). However, ambiguity persists regarding the importance of IMCL as a metabolic substrate for energy production in obesity. A better understanding of the factors regulating FAO, body fat distribution and IMCL mobilisation is important for the development of interventions allowing effective treatment of conditions in which these are disturbed. The study of individuals with metabolic myopathies can give more information about the energy metabolism of muscle. McArdle disease (MD) affects glucose availability to muscle for energy production. Investigations into IMCL storage and mobilisation in MD have not been reported. The aims of this thesis are to investigate 1) the effects of weight-loss via dietary restriction plus modest but clinically-relevant exercise training on FAO, body fat distribution and mobilisation of IMCL during exercise in obese non-diabetic adults; 2) the effect of an exercise training intervention on IMCL storage and mobilisation in a subject with MD. All obese subjects underwent a 4 month lifestyle intervention with weekly meetings with a dietitian and an exercise physiologist. Of the 92 subjects, 73 completed the intervention. They showed significant decreases in body weight (8%), fat mass (14%) and total cholesterol (5%). The exercise prescription of 1500 kcal.week-1 resulted in variable compliance with the prescription (1224 ± 1085 kcal.week-1) measured by heart rate monitor. Those who did most exercise and also those who had less weekly variability in their exercise, had greater reductions in body weight and fat mass. The total activity energy expenditure measured by accelerometry did not change post-intervention but there was a reduction in low intensity activity and an increase in moderate and high intensity activity. A submaximal treadmill test and resting metabolic rate (RMR) using indirect calorimetry was measured before and after the intervention to investigate factors regulating FAO and energy expenditure. Subjects showed increases in FAO without change in energy expenditure for the same walking speed post intervention, but the volume of exercise completed during the intervention was not associated with these changes. To investigate body fat distribution in obesity, VAT, IHL and soleus muscle IMCL was measured in a sub-group of 18 males by magnetic resonance imaging (MRI) and spectroscopy (MRS) along with measurement of maximal aerobic capacity. Fitness increased significantly with significant decreases in VAT (29%) and IHL (54%), without significant change in IMCL. Subjects who had the greatest decrease in VAT were those who exercised for longer durations during the intervention. IHL was the only measure of excess lipid that correlated with IR. The measurement of IMCL before and after 1-hour of cycle ergometer exercise showed no significant mobilisation of IMCL either at baseline or after the lifestyle intervention. The intensity of the acute exercise was adjusted to correspond to each individual’s maximal fatty acid oxidation (MFAO) which increased by over 60% post intervention. In the subject with MD, an 8 week exercise training intervention without dietary intervention increased IMCL stores by 27%, but there was no marked change in IMCL with acute exercise at both time points. The findings of this thesis demonstrate that a clinically relevant and achievable lifestyle intervention incorporating weight loss through diet and objectively measured exercise can achieve improvements in blood lipid profile, body composition and FAO. The differential effects of the intervention on the various fat depots and their associations to metabolic markers suggest that individualised strategies may be required dependent upon body fat distribution. The non detection of mobilisation of IMCL by MRS suggests that these lipids may not be present as a substrate source in this population but rather an ectopic lipid depot related to increased energy consumption in diet. The relatively low capacity for FAO in both the obese and MD subjects may have affected the results. This thesis discusses implications for clinical practice, discusses novel findings related to the energy metabolism in obesity and MD and informs clinical and basic science about important future directions.
| Identifer | oai:union.ndltd.org:ADTP/254210 |
| Creators | Stephanie Ipavec Levasseur |
| Source Sets | Australiasian Digital Theses Program |
| Detected Language | English |
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