| Summary: | Thesis (Ph.D.)--Memorial University of Newfoundland, 1997. Biochemistry Bibliography: leaves 215-237 We hypothesized that EPA is preferentially metabolized in peripheral tissues thus making less of this acid available for storage. The three proposed mechanisms investigated to explain how EPA is preferentially utilized included; 1) EPA is oxidized at a greater rate relative to DHA in skeletal and cardiac muscle, 2) EPA is preferentially hydrolyzed from circulating triacylglycerols, and/or 3) EPA is selectively secreted in bile by the liver. -- To investigate the first proposal, fatty acid oxidation studies were conducted using soleus muscle homogenates, intact soleus muscle and cardiac myocytes. Our findings indicated that even though the rate of oxidation of EPA over DHA was doubled in the experiments which employed soleus muscle homogenates, there was no differential oxidation between EPA and DHA in muscle when these fatty acids were incubated with either the intact soleus muscle or cardiac myocytes. Since the latter two experiments are more representative of the physiological state, it appears that these results do not support our first postulated mechanism that EPA is preferentially oxidized compared to DHA by muscle. -- We also suggested that EPA is preferentially hydrolyzed compared to DHA from circulating triacylglycerols by muscle LPL with the hypothesis that if more EPA is released to the peripheral tissues for metabolism then less would be available for storage in adipose tissue. Therefore, chylomicrons were incubated with cardiac lipoprotein lipase (LPL) to determine if there was selective release of EPA. This study demonstrated no difference in the hydrolysis pattern of the two n-3 fatty acids. Thus, preferential release of EPA from chylomicrons by LPL does not appear to explain the lower storage of EPA in adipose tissue. -- The third mechanism examined the proposal that supplementation of fish oil in the diet results in more EPA compared to DHA being available for hepatic phospholipid synthesis. Consequently, more EPA is secreted in bile by the liver. In this part of the investigation, we determined the fatty acid profile as well as the proportion of fatty acids of phospholipids secreted in the bile of rats being fed a diet containing MaxEPA oil as its primary fat source. Even though biliary phospholipids were enriched in the long chain n-3 fatty acids found in dietary fish oils, no significant difference in the relative proportion of EPA and DHA was observed. The differential storage of DHA compared to EPA is thus, not due to the selective secretion of EPA into bile by the liver. -- From our data, we were able to conclude that the suggested mechanisms are not responsible for the preferential metabolism of EPA relative to DHA. We found that EPA was oxidized at a greater rate than DHA in soleus muscle homogenates. However, when more physiological models were used, i.e., cardiac myocytes or the intact skeletal muscle, there were no differences in the oxidation of either of these fatty acids. Furthermore, we determined that EPA and DHA were released from triacylglycerols in lymph-derived chylomicrons at similar rates and that both fatty adds were secreted in bile to the same extent.
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