Abstract
The polyunsaturated nature of n-3 fatty acids makes them prone to oxidative damage. However, it is not clear if n-3 fatty acids are simply a passive site for oxidative attack or if they also modulate mitochondrial reactive oxygen species (ROS) production. The present study used fat-1 transgenic mice, that are capable of synthesizing n-3 fatty acids, to investigate the influence of increases in n-3 fatty acids and resultant decreases in the n-6∶n-3 ratio on liver mitochondrial H2O2 production and electron transport chain (ETC) activity. There was an increase in n-3 fatty acids and a decrease in the n-6∶n-3 ratio in liver mitochondria from the fat-1 compared to control mice. This change was largely due to alterations in the fatty acid composition of phosphatidylcholine and phosphatidylethanolamine, with only a small percentage of fatty acids in cardiolipin being altered in the fat-1 animals. The lipid changes in the fat-1 mice were associated with a decrease (p<0.05) in the activity of ETC complex I and increases (p<0.05) in the activities of complexes III and IV. Mitochondrial H2O2 production with either succinate or succinate/glutamate/malate substrates was also decreased (p<0.05) in the fat-1 mice. This change in H2O2 production was due to a decrease in ROS production from ETC complex I in the fat-1 animals. These results indicate that the fatty acid changes in fat-1 liver mitochondria may at least partially oppose oxidative stress by limiting ROS production from ETC complex I.
Highlights
Considerable interest exists in the possible health benefits of increasing dietary intake of n-3 fatty acids
There were no significant differences in the relative amounts of these phospholipids from control and fat-1 mitochondria (Table S1)
The purpose of this study was to use transgenic fat-1 mice to investigate the influence of increased n-3 fatty acid levels on mitochondrial reactive oxygen species (ROS) production and electron transport chain (ETC) enzyme activity
Summary
Considerable interest exists in the possible health benefits of increasing dietary intake of n-3 fatty acids. It has been reported that diets high in n-3 fatty acids can decrease the incidence of several disease processes, including coronary heart disease [1,2], inflammatory disorders [3], hypertension, and arthritis [1], as well as some mood disorders [4]. The polyunsaturated nature of n-3 fatty acids makes them susceptible to oxidative damage and it has been reported that supplementing rat diets with docosahexanoic acid (DHA; 22:6 n-3) increases lipid peroxidation in the liver and kidneys [5]. Several factors, including rate of reactive oxygen species (ROS) production and levels of antioxidants can influence oxidative stress, and the lipid environment around membrane proteins which produce ROS may be important in determining the physiological response to n-3 fatty acids (or changes in the n-6:n-3 ratio)
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