Brain protection by rapeseed oil in magnesium-deficient mice

Diets given for 30 days with various mono-(MUFA) and poly-(PUFA) unsaturated fatty acid contents were evaluated for brain protection in magnesium-deficient mice: a commercial and three synthetic diets (n-6PUFA, n-3PUFA and MUFA-based chows enriched with 5% corn/sunflower oils 1:3, with 5% rapeseed oil and with 5% high oleic acid sunflower oil/sunflower oil 7:3, respectively). Unlike magnesium deprivation, they induced significant differences in brain and erythrocyte membrane phospholipid fatty acid compositions. n-3PUFA but not other diets protected magnesium-deficient mice against hyperactivity and moderately towards maximal electroshock- and NMDA-induced seizures. This diet also inhibited audiogenic seizures by 50%, preventing animal deaths. Because, like n-6PUFA diet, matched control MUFA diet failed to induce brain protections, alpha-linolenate (ALA) rather than reduced n-6 PUFA diet content is concluded to cause n-3PUFA neuroprotection. Present in vivo data also corroborate literature in vitro inhibition of T type calcium channels by n-3 PUFA, adding basis to ALA supplementation in human anti-epileptic/neuroprotective strategies.     

Gender-related long-term effects in adult rats by perinatal dietary ratio of n-6/n-3 fatty acids

Epidemiological studies in humans have shown that perinatal nutrition affects health later in life. We have previously shown that the ratio of n-6 to n-3 polyunsaturated fatty acids (PUFA) in the maternal diet affects serum leptin levels and growth of the suckling pups. The aim of the present study was to investigate the long-term effects of various ratios of the dietary n-6 and n-3 PUFA during the perinatal period on serum leptin, insulin, and triacylglycerol, as well as body growth in the adult offspring. During late gestation and throughout lactation, rats were fed an isocaloric diet containing 7 wt% fat, either as linseed oil (n-3 diet), soybean oil (n-6/n-3 diet), or sunflower oil (n-6 diet). At 3 wk of age, the n-6/n-3 PUFA ratios in the serum phospholipids of the offspring were 2.5, 8.3, and 17.5, respectively. After weaning, all pups were given a standard chow. At the 28th postnatal wk, mean body weight and fasting insulin levels were significantly increased in the rats fed the n-6/n-3 diet perinatally compared with the other groups. The systolic blood pressure and serum triacylglycerol levels were only increased in adult male rats of the same group. These data suggest that the balance between n-6 and n-3 PUFA during perinatal development affects several metabolic parameters in adulthood, especially in the male animals.     

Fatty acid composition of membrane bilayers: Importance of diet polyunsaturated fat balance

In one of the most extensive analyses to date we show that the balance of diet n-3 and n-6 polyunsaturated fatty acids (PUFA) is the most important determinant of membrane composition in the rat under 'normal' conditions. Young adult male Sprague-Dawley rats were fed one of twelve moderate-fat diets (25% of total energy) for 8weeks. Diets differed only in fatty acid (FA) profiles, with saturate (SFA) content ranging 8-88% of total FAs, monounsaturate (MUFA) 6-65%, total PUFA 4-81%, n-6 PUFA 3-70% and n-3 PUFA 1-70%. Diet PUFA included only essential FAs 18:2n-6 and 18:3n-3. Balance between n-3 and n-6 PUFA is defined as the PUFA balance (n-3 PUFA as % of total PUFA) and ranged 1-86% in the diets. FA composition was measured for brain, heart, liver, skeletal muscle, erythrocytes and plasma phospholipids, as well as adipose tissue and plasma triglycerides. The conformer-regulator model was used (slope=1 indicates membrane composition completely conforming to diet). Extensive changes in diet SFA, MUFA and PUFA had minimal effect on membranes (average slopes 0.01, 0.07, 0.07 respectively), but considerable influence on adipose tissue and plasma triglycerides (average slopes 0.27, 0.53, 0.47 respectively). Diet balance between n-3 and n-6 PUFA had a biphasic influence on membrane composition. When n-3 PUFA<10% of total PUFA, membrane composition completely conformed to diet (average slope 0.95), while diet PUFA balance>10% had little influence (average slope 0.19). The modern human diet has an average PUFA balance ~10% and this will likely have significant health implications.     

High dose of an n-3 polyunsaturated fatty acid diet lowers activity of C57BL/6 mice

n-3 Polyunsaturated fatty acids (PUFA) are increasingly consumed as food additives and supplements; however, the side effects of these fatty acids, especially at high doses, remain unclear. We previously discovered a high fat n-3 PUFA diet made of fish/flaxseed oils promoted significant weight gain in C57BL/6 mice, relative to a control, without changes in food consumption. Therefore, here we tested the effects of feeding mice high fat (HF) and low fat (LF) n-3 PUFA diets, relative to a purified control diet (CD), on locomotor activity using metabolic cages. Relative to CD, the HF n-3 PUFA diet, but not the LF n-3 PUFA diet, dramatically reduced ambulatory, rearing, and running wheel activities. Furthermore, the HF n-3 PUFA diet lowered the respiratory exchange ratio. The data suggest mixed fish/flaxseed oil diets at high doses could exert some negative side effects and likely have limited therapeutic applications.     

Lipid composition of lactational diets influences the fatty acid profile of the progeny before and after suckling

The purpose of the present study was to compare the influence of adding no or 8% fat of varying sources (coconut oil, fish oil, rapeseed oil and sunflower oil) to diets for sows 1 week prior to farrowing and during lactation on the composition of fatty acids in plasma and tissues of the progeny while sucking and 3 weeks after weaning from the sow. A control diet without supplemental fat and four diets supplemented with 8% of coconut oil, rapeseed oil, fish oil or sunflower oil were provided to lactating sows (n = 15), and during the post-weaning period the same weaner diet was provided to all piglets (n = 15 litters), which were housed litterwise. The dietary ratio of n-6:n-3 fatty acids of the maternal diets largely influenced the progeny, as the ratio varying from 1.2 (fish oil) to 12.2 (sunflower oil) in the sow milk was reflected in plasma and adipose tissues of the sucking progeny. The liver showed similar variations according to dietary treatments, but a lower n-6:n-3 fatty acids ratio. From day 4 to later on during the suckling period, the concentration of C14:0, C16:0 and C18:1 in the liver of the piglets decreased, irrespective of the dietary treatments of sows. In plasma and liver, the total concentration of saturated fatty acids (SAFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) did not differ markedly in piglets sucking sows fed different dietary fatty acids, whereas the adipose tissue of piglets sucking sows fed sunflower oil and coconut oil showed the highest proportion of PUFA and SAFA, respectively. Weaning lowered the concentration of lipid-soluble extracts in plasma and the concentration of fatty acids in the liver of the piglets. Within the post-weaning period, dietary treatments of sows, rather than age of piglets, influenced the fatty acid composition of plasma and adipose tissue of the piglets, whereas the hepatic fatty acid profile was more affected by the age of the piglets during the post-weaning period. This study shows that the fatty acid profile of plasma and tissues of the progeny is highly dependent on the maternal dietary composition, and that the dietary impact persists for up to 3 weeks after the suckling period.     

Leptin levels in rat offspring are modified by the ratio of linoleic to alpha-linolenic acid in the maternal diet

The supply of polyunsaturated fatty acids (PUFA) is important for optimal fetal and postnatal development. We have previously shown that leptin levels in suckling rats are reduced by maternal PUFA deficiency. In the present study, we evaluated the effect of maternal dietary intake of (n-3) and (n-6) PUFA on the leptin content in rat milk and serum leptin levels in suckling pups. For the last 10 days of gestation and throughout lactation, the rats were fed an isocaloric diet containing 7% linseed oil (n-3 diet), sunflower oil (n-6 diet), or soybean oil (n-6/n-3 diet). Body weight, body length, inguinal fat pad weight, and adipocyte size of the pups receiving the n-3 diet were significantly lower during the whole suckling period compared with n-6/n-3 fed pups. Body and fat pad weights of the n-6 fed pups were in between the other two groups at week one, but not different from the n-6/n-3 group at week 3. Feeding dams the n-3 diet resulted in decreased serum leptin levels in the suckling pups compared with pups in the n-6/n-3 group. The mean serum leptin levels of the n-6 pups were between the other two groups but not different from either group. There were no differences in the milk leptin content between the groups. These results show that the balance between the n-6 and n-3 PUFA in the maternal diet rather than amount of n-6 or n-3 PUFA per se could be important for adipose tissue growth and for maintaining adequate serum leptin levels in the offspring.     

A Metabolomic Analysis of Omega-3 Fatty Acid-Mediated Attenuation of Western Diet-Induced Nonalcoholic Steatohepatitis in LDLR -/- Mice

Background

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease and a risk factor for cirrhosis, hepatocellular carcinoma and liver failure. Previously, we reported that dietary docosahexaenoic acid (DHA, 22:6,n-3) was more effective than eicosapentaenoic acid (EPA, 20:5,n-3) at reversing western diet (WD) induced NASH in LDLR^-/- mice.

Methods

Using livers from our previous study, we carried out a global non-targeted metabolomic approach to quantify diet-induced changes in hepatic metabolism.

Results

Livers from WD + olive oil (WD + O)-fed mice displayed histological and gene expression features consistent with NASH. The metabolomic analysis of 320 metabolites established that the WD and n-3 polyunsaturated fatty acid (PUFA) supplementation had broad effects on all major metabolic pathways. Livers from WD + O-fed mice were enriched in saturated (SFA) and monounsaturated fatty acids (MUFA), palmitoyl-sphingomyelin, cholesterol, n-6 PUFA, n-6 PUFA-containing phosphoglycerolipids, n-6 PUFA-derived oxidized lipids (12-HETE) and depleted of C_20-22 n-3 PUFA-containing phosphoglycerolipids, C_20-22 n-3 PUFA-derived oxidized lipids (18-HEPE, 17,18-DiHETE) and S-lactoylglutathione, a methylglyoxal detoxification product. WD + DHA was more effective than WD + EPA at attenuating WD + O-induced changes in NASH gene expression markers, n-6 PUFA and oxidized lipids, citrate and S-lactosyl glutathione. Diet-induced changes in hepatic MUFA and sphingolipid content were associated with changes in expression of enzymes involved in MUFA and sphingolipid synthesis. Changes in hepatic oxidized fatty acids and S-lactoylglutathione, however, correlated with hepatic n-3 and n-6 C_20-22 PUFA content. Hepatic C_20-22 n-3 PUFA content was inversely associated with hepatic α-tocopherol and ascorbate content and positively associated with urinary F2- and F3-isoprostanes, revealing diet effects on whole body oxidative stress.

Conclusion

DHA regulation of hepatic SFA, MUFA, PUFA, sphingomyelin, PUFA-derived oxidized lipids and S-lactoylglutathione may explain the protective effects of DHA against WD-induced NASH in LDLR^-/- mice.     

The effect of dietary fish oils on eicosanoid biosynthesis in peritoneal macrophages is influenced by both dietary N-6 polyunsaturated fats and total dietary fat

Recent research has implicated dietary fish oils in the reduction of eicosanoids formed from arachidonic acid and amelioration of chronic diseases such as coronary heart disease, atherosclerosis and inflammation. Feeding studies were conducted to determine if the efficacy of dietary n-3 polyunsaturated fatty acids (PUFA) from fish oils was influenced by the quantity of n-6 polyunsaturated fatty acids and the total level of fat in the diet. Groups of mice were fed diets composed of 5 and 20% total fat with varying proportions of linoleic acid as a source of n-6 PUFA. Menhaden oil as a source of n-3 PUFA was fed at two levels of n-6 at each level of total fat. Eicosanoid biosynthesis was stimulated and assayed in the mouse peritoneum using zymosan as an inflammatory stimulus. Production of LTE4 and PGE2 was enhanced by increasing n-6 PUFA in the diet at both levels of total fat. High dietary fat significantly suppressed leukotriene (LT) synthesis. Dietary menhaden oil reduced LTE4 and PGE2 synthesis at both levels of dietary n-6 in the low fat study. In animals on 20% dietary fat menhaden oil significantly reduced LT synthesis only at a relatively low dietary n-6 PUFA. On a high n-6 PUFA high fat diets, menhaden oil did not significant affect LTE4 synthesis in response to zymosan stimulation. The results suggest that the effectiveness of fish oils in reducing eicosanoids in response to specific stimulation is influenced by the level of n-6 and the total quantity of fat in the diet.     

Interactive effects of dietary (n-3) polyunsaturated fatty acids and chronic ethanol intoxication on synaptic membrane lipid composition and fluidity in rats.

The influence of dietary polyunsaturated fatty acids on fatty acid composition, cholesterol and phospholipid content as well as 'fluidity' (assessed by fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) probes) of brain synaptic plasma membranes (SPM) and their interactions with chronic ethanol effects were studied in rats fed for two generations with diets either devoid of (n-3) fatty acids (sunflower oil diet), rich in alpha-linolenic acid (soya oil diet) or in long chain (n-3) fatty acids (sunflower + cod liver oil diet). Results were compared with rats fed standard lab chow. Sunflower oil led to an increase in the (n-6)/(n-3) ratio in the membranes with an increase of the 'fluidity' at membrane apolar level; sunflower + cod liver oil decreased the (n-6)/(n-3) ratio without affecting membrane 'fluidity' while no difference was seen between the SPM of rats fed soya oil and standard diet. After 3 weeks alcohol intoxication in rat fed the standard diet: oleic alpha-linoleic acids and cholesterol levels were increased, arachidonic acid and the double bond index/saturated fatty acids were decreased and there was a decrease of 'fluidity' in the lipid core of the SPM. Soya oil almost totally abolished these usually observed changes in the SPM fatty acids composition but increased oleic acid and cholesterol without any change in fluidity. Sunflower oil led to the same general alterations of fatty acid as seen with standard diet but to a greater extent, with decrease of the 'fluidity" at the apolar level and in the region probed by TMA-DPH. When sunflower oil was supplemented with cod liver oil, oleic and alpha-linoleic acids were increased while the 'fluidity' of the apolar core of SPM was decreased. So, the small changes in fatty acid pattern seem able to modulate neural properties i.e. the responses to a neurotoxic like ethanol. A structurally specific role of PUFA is demonstrated by the pernicious effects of the alpha-linolenic acid deficient diet which are not totally prevented by the supply of long chain (n-3) PUFA.     

Effect of different contents of extruded linseed in the sow diet on piglet fatty acid composition and hepatic desaturase expression during the post-natal period

n-3 polyunsaturated fatty acids (n-3 PUFA) contribute to the normal growth and development of numerous organs in the piglet. The fatty acid composition of piglet tissues is linked to the fatty acid composition of sow milk and, consequently, to the composition of sow diet during the gestation and lactation period. In this study, we investigated the impact of different contents of extruded linseed in the sow diet on the fatty acid composition and desaturase gene expression of piglets. Sows received a diet containing either sunflower oil (low 18:3n-3 with 18:3n-3 representing 3% of total fatty acids) or a mixture of extruded linseed and sunflower oil (medium 18:3n-3 with 9% of 18:3n-3) or extruded linseed (high 18:3n-3 with 27% of 18:3n-3) during gestation and lactation. Fatty acid composition was evaluated on sow milk and on different piglet tissues at days 0, 7, 14, 21 and 28. The postnatal evolution of delta5 (D5D) and delta6 (D6D) desaturase mRNA expression was also measured in the liver of low 18:3n-3 and high 18:3n-3 piglets. The milk of high 18:3n-3 sows had higher proportions of n-3PUFA than that of low 18:3n-3 and medium 18:3n-3 sows. Piglets suckling the high 18:3n-3 sows had greater proportions of 18:3n-3, 20:5n-3, 22:5n-3 and 22:6n-3 in the liver, and of 22:5n-3 and 22:6n-3 in the brain than low 18:3n-3 and medium 18:3n-3 piglets. D5D and D6D mRNA expressions in piglet liver were not affected by the maternal diet at any age. In conclusion, extruded linseed in the sow diet modifies the n-3PUFA status of piglets during the postnatal period. However, a minimal content of 18:3n-3 in the sow diet is necessary to increase the n-3PUFA level in piglet liver and brain. Moreover, modifications in the n-3PUFA fatty acid composition of piglet tissue seem linked to the availability of 18:3n-3 in maternal milk and not to desaturase enzyme expression.     

Seizure resistance in fat-1 transgenic mice endogenously synthesizing high levels of omega-3 polyunsaturated fatty acids

n-3 polyunsaturated fatty acids (PUFA), derived from marine oils, have been shown to protect against various neurological diseases. However, very little is known about their potential anticonvulsant properties. The objective of the present study was to determine whether enrichment of brain lipids with n-3 PUFA inhibits seizures induced by pentylenetetrazol. We demonstrate that increased brain levels of n-3 PUFA in transgenic fat-1 male mice, which are capable of de novo synthesis of n-3 PUFA from n-6 PUFA, increases latency to seizure onset by 45%, relative to wildtype controls ( p  = 0.08). Compared with wildtype littermates, transgenic fat-1 mice have significantly ( p  < 0.05) higher levels of docosahexaenoic acid and total n-3 PUFA in brain total lipid extracts and phospholipids. Levels of brain docosahexaenoic acid were positively correlated to seizure latency ( p  < 0.05). These findings demonstrate that n-3 PUFA have anticonvulsant properties and suggest the possibility of a novel, non-drug dietary approach for the treatment of epilepsy.     

Dietary polyunsaturated fatty acids alter myocardial protein kinase C expression and affect cardioprotection induced by chronic hypoxia

We examined the influence of dietary fatty acid (FA) classes on the expression of protein kinase C (PKC) delta and epsilon in relation to the cardioprotective effects of chronic intermittent hypoxia (CIH). Adult male Wistar rats were fed a nonfat diet enriched with 10% lard (saturated FA [SFA]), fish oil (n-3 polyunsaturated FA [n-3 PUFA]), or corn oil (n-6 PUFA) for 10 weeks. After 4 weeks on the diet, each group was divided into two subgroups that were either exposed to CIH in a barochamber (7000 m, 8 hrs/ day) or kept at normoxia for an additional 5-6 weeks. A FA phospholipid profile and Western blot analysis of PKC were performed in left ventricles. Infarct size was assessed in anesthetized animals subjected to 20-min coronary artery occlusion and 3-hr reperfusion. CIH decreased the n-6/n-3 PUFA ratio in all groups by 23% independently of the initial value set by various diets. The combination of n-3 diet and CIH had a stronger antiarrhythmic effect during reperfusion than the n-3 diet alone; this effect was less pronounced in rats fed the n-6 diet. The normoxic n-6 group exhibited smaller infarctions (by 22%) than the n-3 group. CIH decreased the infarct size in n-3 and SFA groups (by 20% and 23%, respectively) but not in the n-6 group. Unlike PKC epsilon, the abundance of PKC delta in the myocardial particulate fraction was increased by CIH except for the n-6 group. Myocardial infarct size was negatively correlated (r=- 0.79) with the abundance of PKC delta in the particulate fraction. We conclude that lipid diets modify the infarct size-limiting effect of CIH by a mechanism that involves the PKC delta-dependent pathway.     

Different edible oil beneficial effects (canola oil, fish oil, palm oil, olive oil, and soybean oil) on spontaneously hypertensive rat glomerular enlargement and glomeruli number

We have tested the different edible oil effects on the blood pressure (BP) control and the following glomerular protection. Six groups of 12-week-old male spontaneously hypertensive rats (SHR) (n = 5), have received different edible oils (fish, canola, palm, olive, and soybean) or a placebo by gavage for 13 weeks. Renal cortex was analyzed through light microscopy and stereology. Usual BP increase, glomerulosclerosis, glomerular enlargement, and glomeruli loss in SHR has been prevented (fish, canola and palm oils) or attenuated (olive and soybean oils) by these oil long-term administration. The most favorable effect has been seen in the fish oil administration (source of n-3 polyunsaturated fatty acids, PUFA, eicosapentaenoic and docosahexaenoic acids), followed by both canola and palm oils (source of n-3 PUFA plus n-9 monounsaturated, MUFA, and saturated fatty acid, respectively), and finally both olive and soybean oils (source of n-9 MUFA and n-6 PUFA, respectively).     

Role of dietary oleic acid from two different sources on fatty acid composition of erythrocyte membrane and blood pressure in healthy subjects

This study has been undertaken to determine the effect of a diet enriched with olive oil (OO) and high-oleic sunflower oil (HOSO) on fatty acid composition of erythrocyte membrane phospholipids and blood pressure in healthy women. OO and HOSO were used as natural sources of monounsaturated fatty acids (MUFAs) in a random-order sequence over two 4-week periods with a 4-week washout period between both MUFA diets. HOSO diet resulted in significant increases in oleic [(18:1n-9) 8.6%, P < 0.001], eicosenoic [(20:1n-9) 33.3%, P < 0.05], arachidonic [(20:4n-6) 6.2%, P < 0.05], and docosapentaenoic [(22:5n-6) 56.0%, P < 0.001] acids, whereas OO diet besides increased the content of stearic acid [(18:0) 13.6%, P < 0.01] and long-chain polyunsaturated fatty acids (PUFAs) of the n-3 family (22:5n-3 and 22:6n-3), when compared with the baseline [a diet high in saturated fatty acids (SFAs) and low in MUFAs]. In contrast, there was a significant decrease in linoleic acid [(18:2n-6) 21.8%, P < 0.001] for both MUFA diets. Consistent with these data, dietary intake of OO significantly raised total PUFAs (7.2%, P < 0.05), the n-3 fatty acids (22.2%, P < 0.01) and the PUFAs/SFAs ratio (9.3%, P < 0.01), as well as decreased the ratio of cholesterol to phospholipids (26,1%, P < 0.001) versus HOSO-based diet. Interestingly, dietary OO, but not HOSO, was able to significantly reduce the systolic (3%, P < 0.05) and diastolic (4%, P < 0.05) blood pressures. Although both vegetable oils provided a similar content of MUFAs (mainly oleic acid), our findings rather indicate that OO has important benefits to modulate the fatty acid composition of membranes and the mechanisms involved in the regulation of blood pressure in human.     

Zinc deficiency and the desaturation of linoleic acid in rats force-fed fat-free diets

Recent studies with rats force-fed zinc-deficient diets containing various types of fat failed to demonstrate a role of zinc in desaturation of linoleic acid. The present study was conducted to investigate the effect of zinc deficiency on desaturation of linoleic acid in rats that were initially force-fed fat-free diets to stimulate activity of desaturases. Therefore, rats were fed zinc-adequate and zinc-deficient fat-free diets for 6 d. After that period, the groups were divided and half of the rats continued feeding the fat-free diet for another 3.5 d whereas the other half was switched to a fat diet by supplementing the fat-free diet with 5% safflower oil. In order to assess desaturation of linoleic acid, fatty acid compositions of liver phosphatidylcholine, ethanolamine, and-serine were considered, particularly levels of individual (n-6) polyunsaturated fatty acids (PUFA). Levels of total and individual (n-6) PUFA were similar in zinc-adequate and zinc-deficient rats fed the fat-free diet throughout the experiment. Addition of 5% safflower oil increased levels of total and individual (n-6) PUFA in both zinc-adequate and zinc-deficient rats. However, total (n-6) PUFA in all types of phospholipids were higher in zinc-adequate rats than in zinc-deficient rats. Additionally, in zinc-deficient rats there were changes of (n-6) PUFA levels typical for impaired Δ5 and Δ6 desaturation: linoleic acid and dihomo-γ-linolenic acid were elevated; arachidonic acid, docosatetraenoic acid, and docosapentaenoic were lowered by zinc deficiency. Therefore, the study shows that zinc deficiency impairs desaturation of linoleic acid in rats force-fed fat-free diets and therefore supports results from former convential zinc deficiency experiments suggesting a role of zinc for desaturation of linoleic acid.     

Effects of dietary polyunsaturated fatty acids and hepatic steatosis on the functioning of isolated working rat heart under normoxic conditions and during post-ischemic reperfusion

The purpose of this study was to modify the amount of 22:4 n-6, 22:5 n-6 and 20:5 n-3 in cardiac phospholipids and to evaluate the influence of these changes on the functioning of working rat hearts and mitochondrial energy metabolism under normoxic conditions and during postischemic reperfusion. The animals were fed one of these four diets: (i) 10% sunflower seed oil (SSO); (ii) 10% SSO + 1% cholesterol; (iii) 5% fish oil (FO, EPAX 3000TG, Pronova) + 5% SSO; (iv) 5% FO + 5% SSO + 1% cholesterol. Feeding n-3 PUFA decreased n-6 PUFA and increased n-3 PUFA in plasma lipids. In the phospholipids of cardiac mitochondria, this dietary modification also induced a decrease in the n-6/n-3 PUFA ratio. Cholesterol feeding induced marked hepatic steatosis (HS) characterized by the whitish appearance of the liver. It also brought about marked changes in the fatty acid composition of plasma and mitochondrial phospholipids. These changes, characterized by the impairment of 5- and 6-desaturases, were more obvious in the SSO-fed rats, probably because of the presence of the precursor of the n-6 family (linoleate) in the diet whereas the FO diet contained large amounts of eicosapentaenoic and docosahexaenoic acids. In the mitochondrial phospholipids of SSO-fed rats, the (22:4 n-6 + 22:5 n-6) to 18:2 n-6 ratio was decreased by HS, without modification of the proportion of 20:4 n-6. In the mitochondrial phospholipids of FO-fed rats, the amount of 20:5 n-3 tended to be higher (+56%). Cardiac functioning was modulated by the diets. Myocardial coronary flow was enhanced by HS in the SSO-fed rats, whereas it was decreased in the FO-fed animals. The rate constant k⁰¹² representing the activity of the adenylate kinase varied in the opposite direction, suggesting that decreased ADP concentrations could cause oxygen wasting through the opening of the permeability transition pore. The recovery of the pump function tended to be increased by n-3 PUFA feeding (+22%) and HS (+45%). However, the release of ascorbyl free radical during reperfusion was not significantly modified by the diets. Conversely, energy production was increased by ischemia/reperfusion in the SSO group, whereas it was not modified in the FO group. This supports greater ischemia/reperfusion-induced calcium accumulation in the SSO groups than in the FO groups. HS did not modify the mitochondrial energy metabolism during ischemia/reperfusion. Taken together, these data suggest that HS- and n-3 PUFA-induced decrease in 22:4 and 22:5 n-6 and increase in 20:5 n-3 favor the recovery of mechanical activity during post-ischemic reperfusion.     

Changes in the fatty acid composition of phospholipids from turbot (Scophthalmus maximus) in relation to dietary polyunsaturated fatty acid deficiencies

Young turbot (1-20 g) were maintained for not less than 14 weeks on three diets: (1) a control diet containing normal amounts of polyunsaturated fatty acids (PUFA); (2) a diet totally deficient in PUFA; (3) a diet deficient in the (n-6) series of PUFA but containing (n-3) PUFA. At 14 weeks the fatty acid compositions of the phospholipids from liver, gut, gills and muscle were analysed. Large changes in the amounts of PUFA in the phospholipids were found. Fish maintained on the totally PUFA deficient diet 2 had retained arachidonic acid, 20:4(n-6), and docosahexaenoic acid, 22:6(n-3), at the expense of eicosapentaenoic acid, 20:5(n-3). Fish maintained on the (n-6) PUFA-deficient diet (3) contained decreased amounts of 20:4(n-6) and 22:6(n-3) while retaining 20:5(n-3). In all cases phosphatidylinositol had the lowest n-3/n-6 ratios. These results are discussed in terms of PUFA function.     

Alteration in Fatty Acid Composition of Adult Rat Brain Capillaries and Choroid Plexus Induced by a Diet Deficient in n-3 Fatty Acids: Slow Recovery After Substitution with a Nondeficient Diet

Wistar rats were fed for three generations with a semisynthetic diet containing either 1.5% sunflower oil (940 mg% of C18:2n-6, 6 mg% of C18:3n-3) or 1.9% soya oil (940 mg% of C18:2n-6, 130 mg% of C18:3n-3). At 60 days of age, the male offspring of the third generation were killed. The fatty acyl composition of isolated capillaries and choroid plexus was determined. The major changes noted in the fatty acid profile of isolated capillaries were a reduction (threefold) in the level of docosahexaenoic acid and, consequently, a fourfold increase in docosapentaenoic acid in sunflower oil-fed animals. The total percentage of polyunsaturated fatty acids was close to that in the soya oil-fed rats, but the ratio of n-3/n-6 fatty acids was reduced by threefold. In the choroid plexus, the C22:6n-3 content was also reduced, but by 2.6-fold, whereas the C22:5n-6 content was increased by 2.3-fold and the ratio of n-3/n-6 fatty acids was reduced by 2.4-fold. When the diet of sunflower oil-fed rats was replaced with a diet containing soya oil at 60 days of age, the recovery in content of n-6 and n-3 fatty acids started immediately after diet substitution; it progressed slowly to reach normal values after 2 months for C22:6n-5 and 2.5 months for C22:6n-3. The recovery in altered fatty acids of choroid plexus was also immediate and very fast. Recovery in content of C22:5n-6 and C22:6n-3 was complete by 46 days after diet substitution.