Year

2011

Degree Name

Doctor of Philosophy

Department

School of Biological Sciences

Abstract

The aim of this thesis was to examine and quantify the influence of diet fatty acid composition on membrane fatty acid composition in the rat, as well as the effect on body composition and metabolic rate. To achieve “normal” conditions (and thus allow best extrapolation to the normal human situation) the rats were young adults from the outbred Sprague Dawley strain to ensure genetic variation. The experimental diets were fed for a reasonable time period of 8 weeks, which is equivalent to ~ one year in humans. The twelve experimental diets were moderate-fat (25% of total energy) and the dominant fats were 18-carbon, which is the normal situation for the diet of both rats and humans.

Diets differed only in their fatty acid profiles, with saturate (SFA) content ranging from 8-88% of total fatty acids, monounsaturate (MUFA) 6-65%, total polyunsaturate (PUFA) 4-81%, n-6 PUFA 3-70% and n-3 PUFA 1-70%. The balance between n-3 and n-6 PUFA is defined as the PUFA balance (n-3 PUFA as % of total PUFA) and ranged 1-86% in the diet. The membrane fatty acid composition was measured for a number of tissues including skeletal muscle, heart, liver, brain, adiposetissue and red blood cells (RBC). In addition, the daily metabolic rate and body composition of each rat was determined.

In these young adult outbred rats fed a moderate-fat diet that included only 18-carbon PUFA, fat profile of the diet had only modest influence on body mass composition and food intake (with higher body fat content associated with increased diet SFA content and elevated food intake related to increased SFA / decreased n-6PUFA content). Of all the metabolic parameters, diet fat profile showed the greatest influence on metabolic rate with a higher mass-specific minimum metabolic rate associated with increased diet n-3 PUFA and PUFA balance.

The conformer/regulator paradigm was used to analyse the results of this study, where the slope of the relationship indicates how responsive the membranes are to diet fat profile. That is, a slope of one indicates the membrane is conforming to diet fat profile while a slope of zero shows that the membrane is strictly regulating fatty acid composition.

This analysis revealed that under “normal” conditions membrane fatty acid composition is in general regulated relatively constant despite extensive changes in diet fatty acid composition (for all tissues except adipose tissue). Diet SFA had essentially no influence on membrane SFA composition (slop≤e0s .02), with a slightly greater response to diet MUFA and PUFA (slopes ≤0.12 and ≤0.09 respectively). Membranes showed a greater responsivity to the individual PUFA classes (n-3 PUFA slopes ≤0.17and n-6 PUFA slopes ≤0.24).

The balance between diet n-3 and n-6 PUFA (PUFA balance), however, showed the greatest effect on membrane composition for all tissues measured. The response to diet PUFA balance was biphasic for most tissues (skeletal muscle, heart, liver, brain and RBC), indicating that a diet PUFA balance of ~10% is the critical level required to maintain membrane PUFA balance. At diet PUFA balances < 10% the membrane PUFA balance of these tissues was highly responsive (slopes of 0.65 – 1.47), indicating that the membranes are essentially completely conforming to diet PUFA balance atthese low levels. Furthermore, reduced membrane PUFA balance was associated with a significantly reduced mass-specific minimum metabolic rate.

One of the major findings of this thesis was the strong influence of diet PUFA balance on membrane arachidonic acid (20:4n-6) content for all tissues. Low diet PUFA balance was associated with significantly increased membrane 20:4n-6 levels. This has potential implications for human health due to the central role membrane 20:4n-6 playsin many parts of metabolic syndrome and chronic inflammation.

If the results from this study in rats also apply to humans, an average PUFA balance of 9.5% in the modern human diet is of considerable concern, as it indicates there are huge numbers of people consuming a diet with a very low and likely inadequate PUFA balance without knowing it.

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