Liver mitochondria isolated from controls or polyunsaturated fatty acid (PUFA) deficient rats were studied for oxidative phosphorylation. A PUFA-deficient diet led to a dramatic change in the fatty acid composition of mitochondrial lipid content, similar to that reported in the literature. Besides the changes in lipid composition, mitochondrial volume was enlarged (+45% in state 4 and two-fold in state 3). State 4 respiration was increased together with a decrease in protonmotive force. The non-ohmicity of the relationship between non-phosphorylating respiration and protonmotive force was more pronounced in the PUFA-deficient group. State 3 oxygen consumption as well as the rate of ATP synthesis showed no difference between the two groups, whereas the protonmotive force decreased substantially in mitochondria from PUFA-deficient animals. In contrast, ATP/O ratios were decreased in the PUFA-deficient group when determined at subsaturating ADP concentration. Taken together, these results are in agreement with both an increased non-ohmic proton leak and an increased redox slipping. The relative importance of these two effects on the overall efficiency of oxidative phosphorylation depends on both the rate of oxidative phosphorylation and the maintained protonmotive force. Hence, in isolated mitochondria the respective role of each effect may vary between state 4 and state 3.
The effects of dietary lipids on the fatty acid composition, activation and proliferation of lymphocytes were investigated. Weanling male Wistar rats were fed for 8 weeks on one of two low-fat diets which contained 50 g lipid/kg, or one of two high-fat diets containing 200 g lipid/kg, from either coconut oil or soyabean oil. The fatty acid composition of phospholipids from splenocyte membranes was affected by dietary lipid manipulation, and these differences influenced lymphocyte functions. Increased levels of linoleic acid in spleen lymphocytes correlated negatively with interleukin-2 receptor α-chain expression determined either by measuring the mean fluorescence or by the proportion of cells staining positive for CD25, and with the cell proliferation index. However, we found a positive correlation between interleukin-2 receptor α-chain expression determined by measuring the mean fluorescence and the cell proliferation index with the oleic acid concentration of spleen lymphocytes. Since phospholipid hydrolysis occurs early in lymphocyte activation, immunosuppressive effects induced by polyunsaturated fatty acids, described in the literature, could be due to an increase of linoleic acid or a decrease of oleic acid affecting many components of plasma-membrane-associated events involved in lymphocyte activation.
Quantitative variations of polyunsaturated fatty acids (PUFA) were studied in various tissues: red blood cells (RBC), hepatic microsomes, kidney, skeletal muscle and heart of young rats fed either a control diet (n = 7) or an essential fatty acid (EFA)-deficient diet (n = 7). After 4 wk, the EFA-[deficient rats had significantly lower proportions of (n-6) and (n-3) fatty acids in RBC, hepatic microsomes and kidney than the control group. Paradoxically, normal proportions of arachidonic acid [20:4(n-6)] and 5,8,11,14,17-eicosapentaenoic acid [20:5(n-3)] were retained in heart and skeletal muscle despite generally lower proportions of the precursors, 18:2(n-6) and 18:3(n-3). Moreover, absolute levels of 20:4(n-6) and 20:5(n-3) in skeletal muscle of the EFA deficient group were significantly higher than in controls and 22:5(n-3) and 22:6(n-3) levels were comparable. This suggests that fatty acid proportions alone, without any consideration of long-chain polyunsaturated fatty acid quantities, may not reflect the (n-6) and (n-3) PUFA status of individual tissues. This study indicates that diet-[induced changes in the PUFA composition of RBC, which are often used in clinical investigations, do not fully reflect the changes in the fatty acid composition of organs, and that individual tissues respond differently to EFA deficiency. The conservation of proportional and absolute levels of 20:5(n-3) and 20:4(n-6), and the decrease in the more unsaturated homologues in the heart, suggest that this organ may avidly retain 20:5(n-3) and 20:4(n-6) in order to maintain eicosanoid production.
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