Docosahexaenoic acid (DHA) might prevent heart failure or optimise drug treatments by improving cardiac contraction. We investigated whether DHA-enriched avian glycerophospholipids (GPL-DHA) exert cardioprotection in ouabain-treated rats after 4 weeks of dietary supplementation with 10, 35 or 60 mg DHA per kg body weight versus none (DHA10, DHA35, DHA60 and control groups, respectively). The contractile responsiveness to different doses of ouabain (10(-7) to 10(-4) M), ouabain intoxication (at 3 × 10(-4) M), and relative variations in cardiac energy metabolism were determined using (31)P NMR in isolated perfused rat hearts. The fatty acid composition of cardiac membranes was analysed by gas chromatography. DHA accretion in the heart was dose-dependent (+8%, +30% and +45% for DHA10, DHA35 and DHA60, respectively). The cardiac phosphocreatine content significantly increased at the baseline in DHA35 (+45%) and DHA60 groups (+85%), and at the different doses of ouabain in the DHA60 group (+73% to 98%). The maximum positive inotropy achieved at 10(-4) M ouabain was significantly increased in all DHA groups versus control (+150%, +122.5% and +135% for DHA10, DHA35 and DHA60, respectively), and ouabain intoxication was delayed. The increase in myocardial phosphocreatine content and the improved efficacy of ouabain on myocardial contraction without toxicity suggest the potential of GPL-DHA as a dietary supplement or ingredient for functional food, and possibly as a co-treatment with digitalis drugs in humans.
Decline in skeletal muscle mass and function starts during adulthood. Among the causes, modifications of the mitochondrial function could be of major importance. Polyunsaturated fatty (ω-3) acids have been shown to play a role in intracellular functions. We hypothesize that docosahexaenoic acid (DHA) supplementation could improve muscle mitochondrial function that could contribute to limit the early consequences of aging on adult muscle. Twelve-month-old male Wistar rats were fed a low-polyunsaturated fat diet and were given DHA (DHA group) or placebo (control group) for 9 wk. Rats from the DHA group showed a higher endurance capacity (+56%, P < 0.05) compared with control animals. Permeabilized myofibers from soleus muscle showed higher O 2 consumptions ( P < 0.05) in the DHA group compared with the control group, with glutamate-malate as substrates, both in basal conditions (i.e., state 2) and under maximal conditions (i.e., state 3, using ADP), along with a higher apparent K m for ADP ( P < 0.05). Calcium retention capacity of isolated mitochondria was lower in DHA group compared with the control group ( P < 0.05). Phospho-AMPK/AMPK ratio and PPARδ mRNA content were higher in the DHA group compared with the control group ( P < 0.05). Results showed that DHA enhanced endurance capacity in adult animals, a beneficial effect potentially resulting from improvement in mitochondrial function, as suggested by our results on permeabilized fibers. DHA supplementation could be of potential interest for the muscle function in adults and for fighting the decline in exercise tolerance with age that could imply energy-sensing pathway, as suggested by changes in phospho-AMPK/AMPK ratio.
Chronic obstructive pulmonary disease (COPD) is associated with patientˈs muscle mass loss and exercise intolerance. An oral supplementation with omega‐3 polyunsaturated fatty acids has been shown to increase exercise capacity in COPD patients. To understand the underlying mechanisms, we studied the effect of docosahexaenoic acid (DHA) oral administration on the muscle function of animals chronically exposed to hypoxia (FiO2 12%) for 3 weeks. Endurance time increased by 210 % in animals under Hypoxia+DHA compared to animals under Hypoxia alone. DHA supplementation preserves the soleus and plantaris muscle masses under Hypoxia despite a similar decrease in total body weight compared to Hypoxia. Oxygen consumption by muscle fibers from soleus using complex I substrate is similar in DHA+Hypoxia and in control (Normoxia) groups but lower in Hypoxia group. This effect of DHA is not seen in white gastrocnemius muscle fibers. Maximal activities and expression levels of respiratory chain complexes are differently affected by Hypoxia and Hypoxia+DHA conditions, suggesting that mitochondria are sensitive to DHA supplementation. These alterations could contribute to the greater exercise tolerance and the muscle mass preservation reported that could justify the use of DHA in patients with muscle mass loss. Further studies are necessary to characterize the action mechanism of DHA on hypoxia‐induced alterations.
The average composition in lipids and fatty acids of the hen's egg is reported. The fact that the egg is a source of phospholipids is pointed out. The enrichment in essential fatty acids in response to different dietary lipids is reported with a focus on enrichment with omega 3 fatty acids. The results of the different approaches of enrichment through seeds oils, marine oils or both are described. The potential interest of using omega 3 enriched egg, specially DHA enriched egg, in human nutrition is documented through the specific properties of DHA-bearing egg phospholipids in terms of stability to oxidation, better bioavailability and specific physiological effects.
The average composition in lipids and fatty acids of the hen's egg is reported. The fact that the egg is a source of phospholipids is pointed out. The enrichment in essential fatty acids in response to different dietary lipids is reported with a focus on enrichment with Omega 3 fatty acids. The results of the different approaches of enrichment through seeds oils, marine oils or both are described. The potential interest of using Omega 3 enriched egg, specially DHA enriched egg, in human nutrition is documented through the specific properties of DHAbearing egg phospholipids in terms of stability to oxidation, better bioavailability and specific physiological effects. (C) 2010 Societe francaise de nutrition. Published by Elsevier Masson SAS. All rights reserved.
A deficiency in essential fatty acid metabolism has been widely reported in both human and animal diabetes. Fish oil supplementations (n-3 fatty acids), containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), were less effective on diabetic neuropathy than (n-6) fatty acids. This partial effect of (n-3) fatty acids might be attributed to the presence of EPA, a competitor of arachidonic acid, which enhanced the diabetes-induced decrease of this fatty acid in serum and tissues. For determining whether a supplementation with DHA alone could prevent neuropathy in streptozotocin-induced diabetes, diabetic rats were given daily, by gavage, liposomes containing DHA phospholipids, at a dose of 60 mg/kg. Eight weeks of diabetes induced significant decreases in nerve conduction velocity (NCV), nerve blood flow (NBF), and sciatic nerve and erythrocyte (red blood cells [RBCs]) Na,K-ATPase activities. DHA phospholipids totally prevented the decrease in NCV and NBF observed during diabetes when compared with the nonsupplemented diabetic group. DHA phospholipids also prevented the Na,K-ATPase activity decrease in RBC but not in sciatic nerve. Moreover, DHA level in sciatic nerve membranes was correlated with NCV. These results demonstrate a protective effect of daily doses of DHA on experimental diabetic neuropathy. Thus, treatment with DHA phospholipids could be suitable for evaluation in clinical trials.
In diabetes, the activity of -6 desaturase, which converts linoleic acid (LA) into -linolenic acid (GLA), the first step of arachidonic acid (AA) synthesis, is decreased, leading to alterations in membrane phospholipid composition. On the other hand, 12 wk after the onset of diabetes, Na ,K -ATPase activity is reduced in many organs, including the kidney. The medullary thick ascending limb (MTAL) reduced Na ,K -ATPase activity, whereas the sodium load secondary to glomerular hyperfiltration was increased. The aim of our study was to examine whether the changes in membrane fatty acid composition resulting from the inhibition of -6 desaturase may be involved in the decreased Na ,K -ATPase activity observed in the outer MTAL after 12 wk of diabetes. GLA is a fatty acid that by-passes the -6 desaturase step. We measured the membrane fatty acid composition and the Na ,K -ATPase activity in the renal outer medulla of control and streptozotocin (STZ)-induced diabetic rats 12 wk after the induction of diabetes. Measurements were performed after supplementation of control rats with sunflower oil (SO) or GLA for 12 wk, and supplementation of 12 wk diabetic rats with SO for 12 wk or with GLA for 6 or 12 wk. Supplementation with GLA not only prevented the decrease in Na ,K -ATPase activity observed after 12 wk of diabetes but also time dependently stimulated Na ,K -ATPase activity in the outer medulla. The changes in Na ,K -ATPase activity were related to parallel changes in the amount of Na ,K -ATPase 1 subunit protein. In addition, in diabetic rats only, Na ,K -ATPase activity was positively correlated with the amount of AA present in cell membranes (r 0.92, P 0.05). Our results indicate that nutritional GLA supplementation increases Na ,K -ATPase activity and expression in diabetic rats. In addition, the positive correlation between AA content and Na ,K -ATPase activity suggests that in diabetic rats, alterations in membrane fatty acid composition contribute to the decreased Na ,K -ATPase activity in outer medulla. J. Nutr. 131: 3160–3165, 2001.
A deficiency in essential fatty acid metabolism has been reported in diabetes. Nutritional supplementations with (n-6) or (n-3) PUFA have differential efficiency on parameters of diabetic neuropathy, including nerve conduction velocity (NCV) and nerve blood flow (NBF). The aim of this study was to compare the neuroprotective effects of gamma-linolenic acid (GLA)-lipoic acid (LA) conjugate (GLA-LA) and docosahexaenoic acid (DHA)-enriched phospholipids (PL) supplementations on NCV and NBF. Streptozotocin-induced diabetic (D) and control (C) rats were supplemented for 8 wk with either DHA-enriched PL at a dose of 30 mg.kg-1.d-1 (DDHA and CDHA) or with corn oil enriched with GLA-LA at a dose of 30 mg.kg-1.d-1 (DGLA and CGLA). Moreover, a C and D group received no supplementation. After 8 wk, NCV (-30%) and NBF (-50%) were lower in the D group than in the C group. Supplementation with GLA-LA totally prevented the decrease in NCV and NBF in the DGLA group, in which values did not differ from group C. Supplementation with DHA only partially prevented the decrease in NCV in the DDHA group, in which value was different from groups C and D and did not affect NBF. We conclude that at the low doses used, supplementation with GLA-LA is more effective than supplementation with DHA in preventing experimental diabetic neuropathy. The difference could be due in part to an antioxidant protective effect of LA on GLA.
Na+/K+-ATPase during diabetes may be regulated by synthesis of its alpha and beta subunits and by changes in membrane fluidity and lipid composition. As these mechanisms were unknown in liver, we studied in rats the effect of streptozotocin-induced diabetes on liver Na+/K+-ATPase. We then evaluated whether fish oil treatment prevented the diabetes-induced changes. Diabetes mellitus induced an increased Na+/K+-ATPase activity and an enhanced expression of the beta1 subunit; there was no change in the amount of the alpha1 and beta3 isoenzymes. Biphasic ouabain inhibition curves were obtained for diabetic groups indicating the presence of low and high affinity sites. No alpha2 and alpha3 isoenzymes could be detected. Diabetes mellitus led to a decrease in membrane fluidity and a change in membrane lipid composition. The diabetes-induced changes are not prevented by fish oil treatment. The results suggest that the increase of Na+/K+-ATPase activity can be associated with the enhanced expression of the beta1 subunit in the diabetic state, but cannot be attributed to changes in membrane fluidity as typically this enzyme will increase in response to an enhancement of membrane fluidity. The presence of a high-affinity site for ouabain (IC50 = 10-7 M) could be explained by the presence of (alphabeta)2 diprotomeric structure of Na+/K+-ATPase or an as yet unknown alpha subunit isoform that may exist in diabetes mellitus. These stimulations might be related, in part, to the modification of fatty acid content during diabetes.
L'adaptation de l'alimentation des poules permet d'obtenir des œufs spécifiquement enrichis en DHA qui ont été utilisés au cours de cette étude sous forme de desserts. Des pensionnaires du Centre de gérontologie ont participé à une étude nutritionnelle de 12 mois visant à suivre les effets d'une supplémentation relativement spécifique en DHA vis-à-vis de FEPA. La composition en acides gras des membranes des érythrocytes et du plasma a été suivie au cours du temps. La population de personnes âgées testée (n-67) présentait un déficit en acide arachidonique (AA) et en DRA dont l'origine semblait indépendante du fonctionnement de la delta 6 désaturase. Vingt-quatre personnes ont été sélectionnées pour l'étude : 16 femmes d'âge moyen 82,5 ans et 8 hommes d'âge moyen 76,5 ans. L'apport quotidien de 100 mg environ de DHA permet d'élever de 30 % le taux de DHA dans l'érythrocyte (7,5 contre 5,7 %) en 3 mois, puis on observe une stabilisation. Le taux d'AA augmente également de 30 % environ (14 à 17,8 %) suivant une cinétique plus lente. Le taux moyen de cholestérol plasmatique ne bouge pas de même que celui des triacylglycérides. La mesure de l'acuité visuelle montre que la vue d'un œil au moins s'est améliorée pour 11 personnes sur 19, qu'une personne n'a pas présenté de changement et que 5 ont montré une baisse d'acuité. En terme d'yeux, sur 32 yeux examinés, 17 ont marqué une amélioration, 6 n'ont pas présenté de variation, 9 ont présenté une diminution de l'acuité.