Effects of alpha-linolenic acid vs. docosahexaenoic acid supply on the distribution of fatty acids among the rat cardiac subcellular membranes after a short- or long-term dietary exposure
Effects of alpha-linolenic acid vs. docosahexaenoic acid supply on the distribution of fatty acids among the rat cardiac subcellular membranes after a short- or long-term dietary exposure
Year: 2009
Authors: Brochot, A. Guinot, M. Auchere, D. Macaire, J.-P. Weill, P. Grynberg, A. Rousseau-Ralliard, D.
Publication Name: Nutrition & Metabolism
Publication Details: Volume 6; Pages 14 – 28.
Abstract:
Previous work showed that the functional cardiac effect of dietary alpha-linolenic acid (ALA) in rats requires a long feeding period (6 months), although a docosahexaenoic (DHA) acid supply affects cardiac adrenergic response after 2 months. However, the total cardiac membrane n3 polyunsaturated fatty acid (PUFA) composition remained unchanged after 2 months. This delay could be due to a specific reorganization of the different subcellular membrane PUFA profiles. This study was designed to investigate the evolution between 2 and 6 months of diet duration of the fatty acid profile in sarcolemmal (SL), mitochondrial (MI), nuclear (NU) and sarcoplasmic reticulum (SR) membrane fractions. Male Wistar rats were randomly assigned to 3 dietary groups (n of 10/diet/period), either n3 PUFA-free diet (CTL), or ALA or DHA rich diets. After 2 or 6 months, the subcellular cardiac membrane fractions were separated by differential centrifugations and sucrose gradients. Each membrane profile was analysed by gas chromatography (GC) after lipid extraction. As expected the n3 PUFA rich diets incorporated n3 PUFA instead of n6 PUFA in all the subcellular fractions, which also exhibited individual specificities. The diet duration increased SFA and decreased PUFA in SL, whereas NU remained constant. The SR and MI enriched in n3 PUFA exhibited a decreased DHA level with ageing in the DHA and CTL groups. Conversely, the n3 PUFA level remained unchanged in the ALA group, due to a significant increase in docosapentaenoic acid (DPA). N3 PUFA rich diets lead to a better PUFA profile in all the fractions and significantly prevent the profile modifications induced by ageing. With the ALA diet the n3 PUFA content, particularly in SR and SL kept increasing between 2 and 6 months, which may partly account for the delay to achieve the modification of adrenergic response. (Authors abstract)
The present study evaluated the hypothesis of a particular rearrangement of the distribution of n3 PUFA among subcellular membranes, depending on the type of the dietary n3 PUFA supplied and the duration. Nuclear (NU), sarcolemmal (SL), mitochondrial (MI) and sarcoplasmic reticulum (SR) membranes were separated in the myocardium of rats fed for 2 or 6 months a diet containing either DHA (from fish oil) or ALA (from linseed flour) to analyse their fatty acid profiles in order to explain the time-related functional effect observed with dietary DHA and ALA. It was hypothesized that the fatty acid composition of the cardiac subcellular membranes, particularly the SR and SL, because of their involvement in antiarrhythmic effects and cardiac excitation-contraction coupling could be differently affected by both dietary supply and duration. The ALA rich diet was effective in increasing the total n3 PUFA during the time course of the experiment, mainly in SR. The difference in n3 PUFA content in plasma membrane (SL) and sarcoplasmic reticulum (SR), both involved in the chronotropic response to adrenergic stimulation, decreased with time between in ALA group and DHA group. n3 PUFA content decreased in the DHA group after 6 months and increased after 2 months in the ALA group. Both ALA and DHA prevented a dietary related alteration of membrane P/S ratio. Among the different membrane fractions investigated, the SR was the richest in PUFA which was preserved throughout the experimental duration. Unlike other membranes, SR displayed a significant cross interaction between duration and diets, in the two n3 PUFA groups. The SR DHA content decreased in DHA fed rats whereas it was maintained and DPA was increased in ALA fed rats. These modifications in SL and SR may affect the activity of ion channels and proteins involved in cardiac β-adrenergic function and calcium signalling. Age-related changes in the activity of these various membrane-bound protein systems were also prevented by long chain n3 PUFA. The present study suggests that the delayed effect of ALA diet (on heart rate and adrenergic response) may be due to the evolution with time of individual subcellular membranes: (i) in SR, the C22 n3 content kept increasing after 6 months of diet with ALA supply but not with DHA supply; (ii) in SL, although decreasing with time, the DHA (and DPA) content remains high enough to account for the regulation of beta-adrenergic receptor function both in ALA group and DHA group. Whatever the membrane fraction considered, DHA and ALA induced a significant rise in membrane unsaturation after 2 months, suggesting an increased membrane fluidity. The authors conclude that there is a need to expand these observations in longer term dietary experiments, in order to investigate a possible dietary impact on health. (Editors Comments)
