Year

2004

Degree Name

Doctor of Philosophy (PhD)

Department

Department of Biomedical Science - Faculty of Health & Behavioural Sciences

Abstract

It has been well established that omega-3 (n-3) polyunsaturated fatty acids (PUFA) (found in fish oil) have beneficial effects on the cardiovascular system including a reduction in ischaemia induced cardiac arrhythmia and increased threshold required to induce electrically ventricular fibrillation. In heart, membrane phospholipid composition reflects dietary fat content. In particular regular fish consumption in humans has been shown to reduce the incidence of new heart attacks, while in rats n-3 PUFA is associated with improved oxygen efficiency and maintained function. In skeletal muscle, membrane composition also reflects dietary fat content. Increased dietary n-3 PUFA has significant effects on skeletal muscle insulin sensitivity and substrate preference amongst a number of other functional changes. The direct effects of n-3 PUFA on skeletal muscle oxygen consumption has not been investigated and may have a significant role in maintaining contractile performance and reducing fatigue. The aim of this thesis was to study the possible direct effects of dietary n-3 PUFA on skeletal muscle oxygen consumption and function in rats. Male Wistar rats (12 weeks old) were fed, ad lib, one of three diets (SF: saturated fat; n-6 PUFA: safflower oil; n-3 PUFA: tuna fish oil) for a period of 8 weeks. The total fat content of the diets was 10% by weight and the level of polyunsaturation in the n-6 and n-3 groups was controlled using a mixture of the test oil and monounsaturated olive oil. After 8 weeks, skeletal muscle oxygen consumption, function and fatigue were assessed using the rat auto-perfused contracting hindlimb developed in this thesis and membrane fatty acids were analysed. The hindlimb auto-perfusion enabled control of blood flow to the animals hindlimb in resting and contracting conditions with simultaneous measurement of oxygen consumption and skeletal muscle twitch tension. The auto-perfusion achieved close to physiologically relevant oxygen consumption and perfusion pressure with a hindlimb flow rate that was reflective of in vivo conditions compared to previously used rat hindlimb perfusion systems. The skeletal muscle membrane composition was reflective of the fat content in the diets. Animals fed n-3 PUFA compared to SF and n-6 PUFA significantly increased total n-3 PUFA, mostly through increased levels of the long chain fat docosahexaenoic acid (DHA) in the membranes. This significantly altered the n-3/n-6 ratio in the membranes. The change in membrane fatty acid composition was very close to previously established changes in the heart after similar dietary interventions, particularly DHA content. The collective results of this thesis support the role of the long chain n-3 PUFA DHA in membranes, as a requirement for optimal skeletal muscle function. In the rat auto-perfused contracting hindlimb, during brief (10minutes) and prolonged (30minutes) bouts of stimulation, in recovery after bouts of stimulation and during hypoxic conditions, n-3 PUFA feeding was associated with enhanced muscle contractile function and indicative of reduced fatigue. Specifically, reduced fatigue in the n-3 PUFA group during normoxic conditions was associated with maintenance of isometric twitch rise time, fall time, contraction duration and maximum rate of tension development and relaxation. The effect of diet on these twitch characteristics provide information that may explain the measured differences in fatigue, such as sarcoplasmic reticulum calcium release. Supportive of the possible changes in skeletal muscle calcium handling was the greater recovery of tension from the fatigued state in n-3 PUFA animals when caffeine was administered. Of particular interest in regard to the hypothesis of this thesis, reduced fatigue in the n-3 PUFA group was associated with modulated oxygen consumption during contraction and recovery. These results complement earlier findings in heart and establish n-3 PUFA DHA in skeletal muscle as an essential membrane fatty acid for optimal function. If human applications of these results are successful, it is most likely that dietary n-3 PUFA may have significant impact on dysfunctional skeletal muscle and improve quality of life. This encompasses muscle function in combination with sedentary life style, diabetes, heart failure, or muscular dystrophy.

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Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.