Effect of sodium loading (3% NaCl) on arachidonic acid biosynthesis in rat liver microsomes

Sodium loading increases arachidonic acid (AA) metabolism by way of the prostaglandins(PGs) from series 2. Its effect on AA biosynthesis remains unknown. The purpose of the present study was to investigate the influence of sodium loading on the fatty acid composition of liver and liver microsomes, and the liver microsomal delta-6 and delta-5 desaturations of linoleic acid (LA) into AA. We found a decrease of LA and dihomo-gamma-linolenic acid (DGLA) levels in liver total lipids of Wistar rats receiving hypernatriuretic drinking water (NaCl 3%) for 60 days. At the same time AA increased. DGLA decreased and AA increased in liver microsomal total lipids. 1(14) C-LA delta-6 desaturase and 2(14)…

Time course of changes in serum oxidant/antioxidant status in overfed obese rats and their offspring.

The aim of the present study was to determine the time course of changes in oxidant/antioxidant status, as well as serum glucose, insulin, leptin and lipid levels, liver adipose tissue and muscle lipid and protein contents, in cafeteria-diet-fed dams during gestation and lactation, and in their offspring throughout adulthood. Food intake was also evaluated. The cafeteria diet induced a significant increase in maternal body and relative adipose tissue weights, daily energy intake, and plasma glucose, insulin, leptin and lipid levels at parturition (day 0) and at the end of lactation (day 21). Plasma total antioxidant status [ORAC (oxygen radical absorbance capacity)], erythrocyte catalase an…

Effect of Dietaryn-3Polyunsaturated Fatty Acids on Oxidant/Antioxidant Status in Macrosomic Offspring of Diabetic Rats

The aim of this work was to determine the effect of dietaryn-3PUFA on oxidant/antioxidant status,in vitrovery low and low density lipoprotein (VLDL-LDL), and VLDL-LDL-fatty acid composition in macrosomic pups of diabetic mothers. We hypothesized thatn-3PUFA would improve oxidative stress in macrosomia. Diabetes was induced in female Wistar rats fed with the ISIO diet (control) or with the EPAX diet (enriched inn-3PUFAs), by streptozotocin. The macrosomic pups were killed at birth (day 0) and at adulthood (day 90). Lipid parameters and VLDL-LDL-fatty acid composition were investigated. The oxidant/antioxidant status was determined by measuring plasma oxygen radical absorbance capacity (ORAC)…

N-3 polyunsaturated fatty acids: An innovative strategy against obesity and related metabolic disorders, intestinal alteration and gut microbiota dysbiosis

Obesity is now widely recognized to be associated with low-grade systemic inflammation. It has been shown that high-fat feeding modulates gut microbiota which strongly increased intestinal permeability leading to lipopolysaccharide absorption causing metabolic endotoxemia that triggers inflammation and metabolic disorders. N-3 polyunsaturated fatty acids (PUFAs) have been shown associated with anti-obesity properties, but results still remain heterogeneous and very few studies underlined the metabolic pathways involved. Thus, the use of Fat-1 transgenic mice allows to better understanding whether endogenous n-3 PUFAs enrichment contributes to obesity and associated metabolic disorders preve…

Membrane fluidity and fatty acid metabolism in kidney cells from rats fed purified eicosapentaenoic acid or purified docosahexaenoic acid

Hagve T-A, Woldseth B, Brox J, Narce M, Poisson J-P. Membrane £uidity and fatty acid metabolism in kidney cells from rats fed puri¢ed eicosapentaenoic acid or puri¢ed docosahexaenoic acid. Scand J Clin Lab Invest 1998; 58: 187^194. Rats were given a supplement (1.5 ml/day) of purified eicosapentaenoic acid (EPA, 20:5,n-3), purified docosahexaenoic acid (DHA, 22:6,n-3)), or corn oil for 10 days. Membrane fluidity, measured as the steady-state fluorescence polarization of diphenylhexatriene (DPH), was approximately 20% lower in kidney cells from rats fed purified EPA than in cells from the DHA-fed or corn-oil fed animals. The level of 20:5(n-3) in kidney phospholipids was 18 times higher in r…

Effects of the association of aging and obesity on lipids, lipoproteins and oxidative stress biomarkers: a comparison of older with young men.

In this study, plasma lipids, lipoproteins and markers of oxidant/antioxidant status were investigated in young (n = 45) and older (n = 40) obese men and compared to those in young (n = 65) and older (n = 55) normal weight controls. The purpose was to determine whether obesity exacerbates or not lipid, lipoprotein abnormalities and oxidative stress in older men. Our findings showed that all obese patients had increased plasma triglyceride, cholesterol, LDL-cholesterol, -triglyceride and HDL-triglyceride levels concentrations compared to controls (P < 0.01). However, the younger obese men had relatively larger and accentuated changes in plasma lipids and lipoproteins than the older patients.…

High pancreatic n-3 fatty acids prevent STZ-induced diabetes in fat-1 mice: inflammatory pathway inhibition.

OBJECTIVE Because of confounding factors, the effects of dietary n-3 polyunsaturated fatty acids (PUFA) on type 1 diabetes remain to be clarified. We therefore evaluated whether fat-1 transgenic mice, a well-controlled experimental model endogenously synthesizing n-3 PUFA, were protected against streptozotocin (STZ)-induced diabetes. We then aimed to elucidate the in vivo response at the pancreatic level. RESEARCH DESIGN AND METHODS β-Cell destruction was produced by multiple low-doses STZ (MLD-STZ). Blood glucose level, plasma insulin level, and plasma lipid analysis were then performed. Pancreatic mRNA expression of cytokines, the monocyte chemoattractant protein, and GLUT2 were evaluate…

Effects of streptozotocin and dietary fructose on delta-6 desaturation in spontaneously hypertensive rat liver.

We have investigated the effects of hypertension associated with diabetes mellitus on polyunsaturated fatty acid biosynthesis. For this purpose, two rat models for these pathologies have been established: a type 1 diabetic hypertensive model obtained by streptozotocin injection to spontaneously hypertensive rat (SHR), followed or not by insulin treatment (experiment 1); a type 2 diabetic hypertensive model by feeding SHR with a fructose enriched diet (experiment 2). Liver gene expression of delta-6 desaturase (D6D), microsomal D6D activities and fatty acid composition of total lipids were estimated. In experiment 1, an increase of linoleic acid (18:2 n-6) level was observed in the streptozo…

Influence of spontaneous hypertension on n-3 delta-6-desaturase activity and fatty acid composition of rat hepatocytes.

The first and rate limiting step in the conversion of alpha-linolenic acid is catalyzed by the delta-6-desaturase enzyme. The activity of such an enzyme was studied in order to investigate the n-3 Polyunsaturated Fatty Acid biogenesis during hypertension. Rat isolated hepatocyte n-3 delta-6-desaturase activity was higher in 1 month old Spontaneously Hypertensive Rats — prehypertensive period- as compared to normotensive Wistar Kyoto rats, whereas there was no significant difference at 12 months — hypertensive period-. Our data indicate no correlation between the directly measured enzyme activity and the changes in hepatocyte n-3 fatty acid compositions. The loss of hepatocyte n-3 delta-6-de…

Long-term use of angiotensin II receptor antagonists and calcium-channel antagonists in Algerian hypertensive patients: Effects on metabolic and oxidative parameters

The effects of calcium antagonists (amlodipine) and angiotensin II receptor antagonists (telmisartan) on lipid profile and oxidative markers were investigated in Algerian hypertensive patients. At the beginning and after 1 year of antihypertensive therapy, blood samples are collected for determination of biochemical parameters (glucose, cholesterol, triglycerides, urea, creatinine) and oxidative markers (malondialdehyde, carbonyl proteins, nitric oxide, superoxide anion, vitamin C, glutathione, catalase, superoxide dismutase). The results of this study indicate that telmisartan and amlodipine are effective antihypertensive agents in the treatment of hypertension because a significant reduct…

Effect of dietary polyunsaturated fatty acids on the expression of peroxisomal ABC transporters

Abstract Peroxisomal ABC transporters encoded by the ABCD genes are thought to participate in the import of specific fatty acids in the peroxisomal matrix. ABCD1 deficiency is associated with X-linked adrenoleukodystrophy (X-ALD), the most frequent peroxisomal disorder which is characterized by the accumulation of saturated very-long-chain fatty acids (VLCFA). ABCD2 (the closest homolog of ABCD1) and ABCD3 have been shown to have partial functional redundancy with ABCD1; only when overexpressed, they can compensate for VLCFA accumulation. Other lipids, for instance polyunsaturated fatty acids (PUFA), should be possible candidate substrates for the ABCD2 and ABCD3 gene products, ALDRP and PM…

Low SOD activity is associated with overproduction of peroxynitrite and nitric oxide in patients with acute coronary syndrome

Abstract Objective The present study was undertaken to evaluate the variation of the oxidative/nitrosative stress status in a population of subjects; with acute coronary syndrome (ACS), and examine its possible implication in plaque rupture which is the main mechanism in the pathophysiology of ACS. Patients and methods We made this study on 50 men with ACS and 50 age and sex matched healthy controls. Nitrosative/oxidative stress markers including; nitric oxide, superoxide anion levels, superoxide dismutase (SOD) activity and peroxynitrite levels were evaluated in blood samples of patients and controls. Results Compared with healthy subjects, coronary patients had significantly higher nitric…

Psychosocial stress, catecholamines, and essential fatty acid metabolism in rats.

To examine the effects of psychosocial stress and the "stress hormone," epinephrine, on essential fatty acid metabolism in rats, two studies were conducted. In the first, the effects of four weeks of (i) social isolation and (ii) group housing (control) on liver microsomal delta 6 and delta 5 n-6 desaturase activity were studied in group-reared male normotensive (Wistar Kyoto) and spontaneously hypertensive (SHR) rats (n = 5/group). The second study examined the effects of acute ip epinephrine (0.0, 1.0, 2.0, and 4.0 mg/kg) 6 hr prior to and following an ig dose (4 g/kg) of safflower oil (rich in 18:2n-6, LA) on plasma and liver LA, 20:4n-6 (AA), and LA/AA ratios in adult essential fatty ac…

Shifted cooperation of desaturation and oxidation of palmitic acid in rat liver

n-3 polyunsaturated fatty acids and HER2-positive breast cancer: interest of the fat-1 transgenic mouse model over conventional dietary supplementation.

Overexpression of the tyrosine kinase receptor ErbB2/HER2/Neu, occurs in 25%-30% of invasive breast cancer (BC) with poor patient prognosis. Even if numerous studies have shown prevention of breast cancer by n-3 fatty acid intake, the experimental conditions under which n-3 fatty acids exert their protective effect have been variable from study to study, preventing unifying conclusions. Due to confounding factors, inconsistencies still remain regarding protective effects of n-3 polyunsaturated fatty acids (PUFA) on BC. When animals are fed with dietary supplementation in n-3 fatty acids (the traditional approach to modify tissue content and decrease the n-6/n-3 ratio) complex dietary intera…

Stearoyl-CoA desaturase 1 coding sequences abd antisense RNA affect lipid secretion in transfected chicken LMH hepatoma cells

Hepatic stearoyl CoA desaturase (SCD) activity in chickens from a fat line is higher than that of chickens from a lean line and correlates with plasma triacylglycerol concentrations. Furthermore, in these lines, the hepatic SCD1 mRNA level is positively correlated with the adipose tissue weight. To analyze the contribution of the SCD1 gene in the regulation of adiposity in the early stages of triacylglycerol secretion, SCD1 coding sequence and antisense RNA expression vectors were transfected in LMH cells. After selection, these cells were analyzed with regard to SCD1 expression and lipid secretion. The amounts of secreted triacylglycerols and phospholipids were shown to be higher in LMH ce…

Liver X receptor activation promotes polyunsaturated fatty acid synthesis in macrophages : relevance in the context of atherosclerosis

Objective— Liver X receptors (LXRs) modulate cholesterol and fatty acid homeostasis as well as inflammation. This study aims to decipher the role of LXRs in the regulation of polyunsaturated fatty acid (PUFA) synthesis in macrophages in the context of atherosclerosis. Approach and Results— Transcriptomic analysis in human monocytes and macrophages was used to identify putative LXR target genes among enzymes involved in PUFA biosynthesis. In parallel, the consequences of LXR activation or LXR invalidation on PUFA synthesis and distribution were determined. Finally, we investigated the impact of LXR activation on PUFA metabolism in vivo in apolipoprotein E–deficient mice. mRNA levels of acyl…

Dehydroepiandrosterone up-regulates the Adrenoleukodystrophy-related gene (ABCD2) independently of PPAR alpha in rodents

International audience; X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease caused by mutations in the ABCD1 gene, which encodes a peroxisomal ABC transporter, ALDP, supposed to participate in the transport of very long chain fatty acids (VLCFA). The adrenoleukodystrophyrelated protein (ALDRP), which is encoded by the ABCD2 gene, is the closest homolog of ALDP and is considered as a potential therapeutic target since functional redundancy has been demonstrated between the two proteins. Pharmacological induction of Abcd2 by fibrates through the activation of PPARa has been demonstrated in rodent liver. DHEA, the most abundant steroid in human, is described as a PPARa activat…

Inhibition of stearoyl-CoA desaturase 1 expression induces CHOP-dependent cell death in human cancer cells.

Background Cancer cells present a sustained de novo fatty acid synthesis with an increase of saturated and monounsaturated fatty acid (MUFA) production. This change in fatty acid metabolism is associated with overexpression of stearoyl-CoA desaturase 1 (Scd1), which catalyses the transformation of saturated fatty acids into monounsaturated fatty acids (e.g., oleic acid). Several reports demonstrated that inhibition of Scd1 led to the blocking of proliferation and induction of apoptosis in cancer cells. Nevertheless, mechanisms of cell death activation remain to be better understood. Principal Findings In this study, we demonstrated that Scd1 extinction by siRNA triggered abolition of de nov…

Trans-10, cis-12 conjugated linoleic acid induced cell death in human colon cancer cells through reactive oxygen species-mediated ER stress

Dietary conjugated linoleic acids (CLA) are fatty acid isomers with anticancer activities produced naturally in ruminants or from vegetable oil processing. The anticancer effects of CLA differ upon the cancer origin and the CLA isomers. In this study, we carried out to precise the effects of CLA isomers, c9,t11 and t10,c12 CLA, on mechanisms of cell death induction in colon cancer cells. We first showed that only t10,c12 CLA treatment (25 and 50μM) for 72h triggered apoptosis in colon cancer cells without affecting viability of normal-derived colon epithelial cells. Exposure of colon cancer cells to t10,c12 CLA activated ER stress characterized by induction of eIF2α phoshorylation, splicing…

Activation of liver x receptors promotes polyunsaturated fatty acid synthesis and eicosanoid secretion in human macrophages

Intestinal microbiota mediates the beneficial effects of n-3 polyunsaturated fatty acids during dietary obesity,

Obesity, now considered as a real worldwide epidemic affecting more than 650 million people, is complex and mainly associated with excessive energy intake and changes in eating habits favoring the consumption of diets rich in saturated fat and sugar. This multifactorial pathology is linked to chronic low grade systemic inflammation. Indeed, a high fat diet (HFD) leads to intestinal microbiota dysbiosis increasing gut permeability (partly attributed to a downregulation of genes encoding tight junction proteins) leading to an increase in bacterial lipopolysaccharides (LPS) levels so-called metabolic endotoxemia. Studies have shown that n-3 polyunsaturated fatty acids (PUFAs) are involved in t…

Fast high performance liquid chromatography analysis in lipidomics: Separation of radiolabelled fatty acids and phosphatidylcholine molecular species using a monolithic C18 silica column

Abstract HPLC procedures using conventional C 18 columns are usually used to separate simple and complex lipid mixtures but these methods of separation remain often laborious and very slow. Here, monolithic columns were successfully applied to separate lipids – radiolabelled fatty acid mixtures and individual phosphatidylcholine (PC) molecular species. For that, isocratic elution was performed using two Chromolith™ Performance RP-18e columns connected in series. Detection was achieved by online measurement of radioactivity for radiolabelled fatty acids and by UV absorbance at 205 nm for PC molecular species. The performances of such silica rods were compared to conventional reverse-phase si…

Method for evaluating the bioconversion of radioactive polyunsaturated fatty acids by use of reversed-phase liquid chromatography

Abstract Reversed-phase high-performance liquid chromatography on a thermostatted octadecylsilyl column was used to separate mixtures of labelled polyunsaturated fatty acids (as their methyl esters) formed by successive desaturations and elongations of labelled linoleic (18:2 n - 6) or linolenic (18:3 n -3) acid by rat liver microsomes. Acetonitrile-water mixtures were used for elution of the esters. Unsaturated and saturated esters were detected by their refractive indices. The order of elution of fatty acid methyl esters in complex mixtures varies as a function of the chain length and unsaturation, analysis temperature, water concentration and solvent flow-rate. The peak areas vary as a f…

Thrombosis factors and oxidant/antioxidant markers in obese and hypertensive women during pregnancy.

To investigate the oxidative profile and thrombotic markers in obese and hypertensive mothers.Thirty obese, 28 hypertensive and 34 healthy control mothers were recruited from Tlemcen Hospital, Algeria. Plasma vitamin C, nitric oxide, superoxide anion, erythrocyte glutathione, malondialdehyde, carbonyl proteins and erythrocyte antioxidant enzyme activities and coagulation markers [protein C, protein S, fibrinogen, prothrombin, antithrombin, activated partial thromboplastin time (APTT), lupus anticoagulants (LACs)] were measured. Changes in plasma urea, creatinine, uric acid, glucose and lipid levels were also determined.Plasma glucose concentrations were high in obese mothers, and plasma ure…

Retinal enrichment in omega-3 polyunsaturated fatty acids limits choroidal neovascularization

International audience; Purpose: Age-related Macular Degeneration (AMD) is the primary cause of blindness in elderly population of western countries. Prospective epidemiologic studies have reported that omega-3 polyunsaturated fatty acids (PUFAs) reduce the risk of progression to advanced AMD, and particularly to the neovascular forms. In this study, we have investigated the beneficial effects of omega-3 PUFA on choroidal neovascularization (CNV) in mice.Methods: Fat-1 mice, endogenously converting omega-6 to omega-3 PUFA, and littermate controls were used at 4 months of age. CNV was induced unilaterally in eye fundus by photocoagulation using a 532-nm laser. Confocal scanning laser ophthal…

Desaturase activities are depleted before and after weaning in liver microsomes of spontaneously hypertensive rats

Abstract In the present study, we have investigated the microsomal linoleic acid desaturation steps into arachidonic acid in 10- and 30-day-old spontaneously hypertensive rats (SHR), as compared to their normotensive control rats, Wistar Kyoto (WKY). Suckled by adoptive Wistar normotensive female, the SHR and WKY were fed the same diet. Our results show lower Δ6 and Δ5 desaturase activities (the limiting steps in the bioconversion of linoleic acid into arachidonic acid) in the young SHR, as compared to the WKY normotensive rats. The fatty acid composition of liver microsomal total lipids evidences a higher proportion of linoleic acid in SHR than in WKY, in agreement with the partially deple…

In vitro effects of vitamins C and E, n-3 and n-6 PUFA and n-9 MUFA on placental cell function and redox status in type 1 diabetic pregnant women.

IF 2.972; International audience; The aim of this investigation was to determine the in vitro effects of vitamin C and E, n-3 and n-6 PUFA and n-9 MUFA on placental cell proliferation and function in type 1 diabetes. Placenta tissues were collected from 30 control healthy and 30 type 1 diabetic women at delivery. Placental cells were isolated and were cultured in RPMI medium supplemented with vitamin C (50 μM), vitamin E (50 μM), n-3 PUFA (100 μM), n-6 PUFA (100 μM) or n-9 MUFA (100 μM). Cell proliferation, cell glucose uptake and intracellular oxidative status were investigated. Our results showed that basal placental cell proliferation, glucose uptake, malondialdehyde (MDA) and carbonyl p…

Liver microsomal membrane fluidity and microsomal desaturase activities in adult spontaneously hypertensive rats.

OBJECTIVE The purpose of the present study was to investigate liver microsomal membrane fluidity simultaneously with membrane fatty acid composition and desaturase activities in spontaneously hypertensive rats (SHR). DESIGN AND METHODS The membrane fluidity was determined, after electron spin resonance (ESR) measurement, in SHR compared with normotensive Wistar-Kyoto (WKY) rats, by calculating the order parameter S from ESR spectra of 5-nitroxide stearate and 10-nitroxide stearate, used as spin-labelled fatty acids. Desaturase activities were measured by incubating SHR and WKY rat liver microsomes with [14C]-radiolabeled fatty acids as substrates for desaturation reactions. The fatty acid c…

Les acides gras trans : des acides gras bien singuliers

Cette revue resume des donnees experimentales ou cliniques recentes sur les acides gras trans, qui permettent de considerer certains d’entre eux comme des molecules bioactives d’interet – en particulier dans le domaine cardiovasculaire et en cancerologie –, susceptibles d’apporter une impulsion nouvelle aux applications industrielles relatives a leurs effets favorables sur la sante. Dans cette revue, nous soulignons l’emergence de divers aspects benefiques des acides gras trans naturels, qui ont des proprietes distinctes et parfois meme opposees a celles des acides gras trans retrouves dans les huiles partiellement hydrogenees. Ainsi, apres avoir ete mis en avant pour leurs effets deleteres…

Fatty acid metabolism, pharmacological nutrients and hypertension.

Abstract The purpose of the present study was to investigate the effect of a concentrated preparation (EPA30) containing eicosapentaenoic acid (EPA. 20:5 n -3) and docosahexaenoic acid (DHA, 22:6 n -3) on the limiting desaturation steps of the polyunsaturated fatty acid biosynthesis in spontaneously hypertensive rats (SHR). Adult SHR were divided into two groups: one group received a standard diet, and the experimental group the standard diet including 0.8% of EPA30 for 9 weeks. Blood pressure was measured at the end of the diets. The desaturase activities and fatty acid composition were determined in isolated hepatocytes. The blood pressure did not decrease in the experimental group. The d…

The effects of alpha-cypermethrin exposure on biochemical and redox parameters in pregnant rats and their newborns

IF 2.388; International audience; Pyrethroid insecticides are extensively used in agriculture and in household activities. During pregnancy, they might affect maternal metabolic status and there after fetal development. In this work, we studied metabolic and redox effects of low dose alpha-cypermethrin exposure in pregnant rats and their offspring. The diet containing alpha cypermethrin at 0.02 mg/kg/day was consumed during the entire gestation. Plasma biochemical parameters as well as liver lipid and oxidative stress markers were determined. Our results showed that alpha-cypermethrin induced an increase in body weight and in plasma glucose and lipid levels, as well as in plasma aspartate a…

Oxidative stress and maternal obesity: Feto-placental unit interaction

Abstract Objective To determine oxidative stress markers in maternal obesity during pregnancy and to evaluate feto-placental unit interaction, especially predictors of fetal metabolic alterations. Patients and methods 40 obese pregnant women (prepregnancy BMI > 30 kg/m²) were compared to 50 control pregnant women. Maternal, cord blood and placenta samples were collected at delivery. Biochemical parameters (total cholesterol and triglycerides) and oxidative stress markers (malondialdehyde, carbonyl proteins, superoxide anion expressed as reduced Nitroblue Tetrazolium, nitric oxide expressed as nitrite, reduced glutathione, catalase, superoxide dismutase) were assayed by biochemical methods. …

Évaluation de la toxicité aiguë de la 2-hydroxy-méthyl-1 (N-phtaloyltryptophyl) aziridine chez le rat Wistar

Objectifs : Les aziridines, molecules alkylantes a l’ADN, possedent une grande activite anticancereuse et antibiotique et modulent le systeme immunitaire. Une nouvelle aziridine, la 2-hydroxy-methyl-1 (N-phtaloyltryptophyl) aziridine, a ete synthetisee dans notre laboratoire. Cependant, sa toxicite n’est pas connue. L’objectif de ce travail est de determiner la toxicite aigue de cette aziridine chez le rat Wistar. Materiel et Methodes : Cinq lots de rats Wistar mâles recoivent une injection intra peritoneale de 9,35 mg/kg, 37,4 mg/kg, 93,5 mg/kg, 140,25 mg/kg, 187 mg/kg d’aziridine, et sont observes pendant 14 jours. Les mortalites, les modifications du comportement, du poids, et les variat…

Age-related changes in antioxidant defence mechanisms and peroxidation in isolated hepatocytes from spontaneously hypertensive and normotensive rats

International audience; The effects of age and hypertension on the antioxidant defence systems and the lipid peroxidation in rat isolated hepatocytes were studied. Four different age groups (1, 3, 6 and 12 months) were considered in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Age-associated changes were observed on vitamin E status, glutathione (GSH) level, MDA formation and glutathione peroxidase (GSH-Px) activity in both strains. Maximal levels or activities of these parameters were found at 3 and 6 months, except for MDA which was low at 3 months. Then, a fall was observed at 12-month-old compared to 6-month values. In addition, GSH-Px activity was sig…

Age-related changes in linoleic acid bioconversion by isolated hepatocytes from spontaneously hypertensive and normotensive rats

This study points out the hepatocyte interconversion of the linoleic acid family during hypertension. Hepatocyte delta 6 desaturase activity was higher in 1 month-old spontaneously hypertensive rats than in normotensive controls. A similar tendency was observed in 6 month-old SHR. delta 5 desaturase activity was higher only in 1 month-old spontaneously hypertensive rats as compared to controls. Desaturase activities were particularly high at the age of 6 months. The hepatocyte fatty acid composition showed an impairment of n-6 polyunsaturated fatty acid metabolism in spontaneously hypertensive animals. Changes were greater in the young prehypertensive rats than in adults. A storage of n-3 l…

Liver oleic acid biogenesis is impaired during the prehypertensive period in the spontaneously hypertensive rat.

In the present study, we have investigated the liver microsomal stearic acid delta9 desaturation, and the fatty acid composition of liver microsomal total lipids in 10- and 30-day-old spontaneously hypertensive rats (SHRs), compared to the normotensive Wistar Kyoto (WKY) control rats. So as to avoid any influence related to the diet, the composition of the milk being different in SHR and WKY strains, the pups were suckled by adoptive normotensive female Wistar. After weaning, the 30-day-old rats were fed a standard commercial diet and then killed. Our results show lower liver microsomal delta9 desaturase activities in the 10- and 30-day-old SHR versus the WKY of the same age. The fatty acid…

Hepatic and very low-density lipoprotein fatty acids in obese offspring of overfed dams.

The combined effects of developmental programming and high-fat feeding at weaning on fatty acid metabolism of the offspring are not well known. In the present study, we aim at characterizing the influence of maternal and offspring's own diets on liver and very low-density lipoprotein (VLDL) lipids; fatty acid profiles of VLDL and liver phospholipids, triglycerides, and cholesteryl esters; and hepatic enzyme activities. Twenty obese male rats born to cafeteria diet-fed dams and 20 control rats born to control diet-fed dams were selected. At weaning, 10 rats of each group were fed control or cafeteria diet. Obese rats had a significant increase in serum glucose, insulin, leptin, VLDL apolipop…

Effects of Mancozeb and Metribuzin on in vitro proliferative responses and oxidative stress of human and rat spleen lymphocytes stimulated by mitogens

Pesticides have been shown to possess marked immunotropic activity. The aim of this work was to study the in vitro effects of different concentrations (1-100 µM) of Mancozeb (fungicide) and Metribuzin (herbicide), on the proliferative responses of human and rat spleen lymphocytes stimulated by concanavalin A (ConA, mitogen), the Th1- (IL-2, INFγ) and Th2- (IL-4) cytokine secretion and on the intracellular oxidative status. The results showed that Mancozeb significantly reduced ConA lymphocyte proliferation in a dose-dependent manner in both humans and rats. It also decreased IL-2, INFγ and IL-4 secretion with a a shift away to Th1 phenotype. Metribuzin at low concentrations (1-10 µM) result…

Inhibition of the HER2 pathway by n-3 polyunsaturated fatty acids prevents breast cancer in fat-1 transgenic mice

Overexpression of the tyrosine kinase receptor, ErbB2/HER2/Neu, occurs in 25–30% of invasive breast cancer (BC) with poor patient prognosis. Due to confounding factors, inconsistencies still remain regarding the protective effects of n-3 polyunsaturated fatty acids (PUFAs) on BC. We therefore evaluated whether fat-1 transgenic mice, endogenously synthesizing n-3 PUFAs from n-6 PUFAs, were protected against BC development, and we then aimed to study in vivo a mechanism potentially involved in such protection. E0771 BC cells were implanted into fat-1 and wild-type (WT) mice. After tumorigenesis examination, we analyzed the expression of proteins involved in the HER2 signaling pathway and lipi…

Les oméga-3 préviennent l’altération de la couche de mucus, le stress du réticulum endoplasmique et l’inflammation induits par un régime obésogène au niveau du colon de souris fat-1

Introduction et but de l’etude Un regime obesogene induit d’importantes alterations de la barriere intestinale, une endotoxemie metabolique et une inflammation chronique dite de bas bruit. La couche de mucus recouvrant l’intestin, principalement constituee de la glycoproteine Muc2 produite par les cellules caliciformes, maintient les bacteries du microbiote a distance des cellules hotes, empechant ainsi une activation du systeme immunitaire. Il a ete montre qu’un regime obesogene etait capable d’alterer l’epaisseur de cette couche de mucus en association avec une inflammation et un stress du reticulum endoplasmique. Les omega-3 exercent de puissants effets anti-inflammatoires, et un enrichi…

Composition en acides gras des hémisphères cérébraux de rats spontanément hypertendus allaités par des femelles Wistar

Total lipid fatty acid composition was investigated in brain hemispheres of male Spontaneously Hypertensive Rats (SHR), compared with normotensive Wistar Kyoto rats (WKY) used as controls. Both strains were suckled by adoptive Wistar mothers, and then fed a standard diet after weaning. No difference was observed between the two hemispheres of WKY killed either at 10 or 30 days. In SHR killed at 10 days, the two hemispheres showed differences, SHR left hemispheres exhibiting greater fatty acid composition changes than those of WKY, phenomenon that toned down at 30 days. Hence, SHR pups showed a different total lipid fatty acid composition of their brain hemispheres when compared with their W…

Depletion of delta 9 desaturase (EC 1.14.99.5) activity in lactating rat during protein restriction.

The effects of protein restriction on the activity of delta9 desaturase (EC 1.14.99.5) were investigated in lactating rats. A control group was fed a balanced diet (20% casein) for 14 days, whereas the experimental groups were fed a low-protein diet (8% casein), supplemented with or without L-methionine (0.4%), for 14 days. The enzyme activity was measured by incubations of hepatic microsomal pellets with (1-14C) stearic acid. Results showed a decreased delta9 desaturase activity, after 2,7 and 14 days of depleted diet, of -50, -40 and -33% respectively, compared with control. The supplementation of the low-protein diet with 0.4% methionine, which favours food consumption as well as growth,…

Revisiting delta-6 desaturase regulation by C18 unsaturated fatty acids, depending on the nutritional status.

Dietary polyunsaturated fatty acids (PUFA) play a key role in regulating delta-6 desaturase (D6D), the key enzyme for long-chain PUFA biosynthesis. Nevertheless, the extent of their effects on this enzyme remains controversial and difficult to assess. It has been generally admitted that C18 unsaturated fatty acids (UFAs) regulate negatively delta-6 desaturase (D6D). This inhibition has been evidenced in regard to a high glucose/fat free (HG/FF) diet used in reference. However, several nutritional investigations did not evidence any inhibition of desaturases when feeding fatty acids. Because the choice of the basal diet appeared to be of primary importance in such experiments, our goal was t…

Desaturation and esterification of fatty acids in kidney cells from spontaneously hypertensive rats

In previous studies, several alterations in lipid metabolism have been related to hypertension, but the mechanisms explaining this relationship have not been elucidated. None of the previous works has focused on the lipid metabolism in kidney, which is a key organ in the overall regulation of blood pressure. The aim of the present work was to study the metabolism of polyunsaturated fatty acids, and the possible compositional changes in kidney from hypertensive rats. Radiolabelled linoleic acid (18:2,n-6) and dihomogammalinolenic acid (20:3, n-6) were incubated with isolated kidney cells from spontaneously hypertensive rats (SHR) or the parent normotensive strain (Wistar Kyoto, WKY). The rat…

Hemostatic, inflammatory, and oxidative markers in pesticide user farmers

Research Article; International audience; The aim of this work was to investigate inflammatory, oxidative, and thrombotic parameters as biomarkers in farmers exposed to pesticides. Fifty farmers using chemical pesticides and 60 unexposed control men participated in this study. The Mediterranean diet compliance, the duration of pesticide use, and personal protection for pesticides handling were recorded using self-administered questionnaires. Serum biochemical parameters, oxidant/antioxidant, inflammatory, and thrombosis markers were determined. Our findings showed oxidative stress reflected by an increase in malondialdehyde, carbonyl proteins and superoxide anion levels and a decrease in vi…

CL046 - Obésité néonatale : Syndrome plurimétabolique et risque athérogène précoce

Objectifs Ce travail consiste a mettre en evidence les marqueurs du risque atherogene et du stress oxydatif chez les nouveau-nes macrosomiques dans le but d’une intervention precoce. Materiel et Methodes Les echantillons de sang proviennent de nouveaunes macrosomiques de meres diabetiques/obeses et de temoins a terme. Sur le sang de cordon et sur le sang preleve a un mois de vie post-natale, les lipides, le pouvoir antioxydant total (ORAC), les activites des enzymes erythrocytaires antioxydantes, les hydroperoxydes et les radicaux carbonyles sont doses par methodes biochimiques; les vitamines plasmatiques A, C et E par HPLC. Resultats Nos resultats montrent que les nouveau-nes macrosomiques…

Adrenic acid Δ4 desaturation and fatty acid composition in liver microsomes of spontaneously diabetic Wistar BB rats

We examined the delta 4 (n-6) desaturation and the fatty acid composition of liver microsomes in the insulin-dependent spontaneously diabetic Wistar Bio-Breeding (BB) rat. The desaturation of adrenic acid to n-6 docosapentaenoic acid was decreased in the normo- and hyperglycemic diabetic rats. Insulin treatment with 1.0 IU. 100 g body weight-1 twice a day for 2 days restored the reduced activity during the hypoglycemic period. The pattern of responses was similar to that of linoleic acid delta 6 and dihomo-gamma-linolenic acid delta 5 desaturases, with a non-parallel relationship between the desaturation system and the glycemia. The microsomal fatty acid composition of BB rat liver reflecte…

Chronic low level metribuzin exposure induces metabolic alterations in rats

Abstract In this work we evaluated the in vivo effects of chronic metribuzin exposure at doses that mimic human exposure through diet. Male and female rats were fed a potato diet containing metribuzin at low doses (D1, 1.3 mg/kg or D2, 13 mg/kg) for 3 months. Plasma biochemical parameters (glucose, lipid, urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST)), as well as lipid and protein contents, markers of oxidative stress in different organs (liver, adipose tissue, muscle, intestine) were determined. Our results showed that exposure to metribuzin induced a significant reduction in body weight, food intake and adverse alterations in biochemical parameters suc…

Altered adipose tissue metabolism in offspring of dietary obese rat dams.

To investigate further the mechanisms of developmental programming, we analysed the effects of maternal overnutrition and of postnatal high-fat feeding on adipose tissue metabolism in the offspring. Postnatal changes in serum adiponectin, leptin and TAG [triacylglycerol (triglyceride)] levels, adipose tissue TAGs, fatty acids and enzyme activities were determined in offspring of cafeteria-diet-fed dams during gestation and lactation, weaned on to standard chow or on to cafeteria diet. Obese rats showed higher adiposity (+35% to 85%) as well as a significant increase in serum glucose, insulin, leptin, adiponectin and TAG levels (P&amp;lt;0.01) and adipose tissue LPL (lipoprotein lipase) and …

In vitro effects of oil's fatty acids on T cell function in gestational diabetic pregnant women and their newborns 油类脂肪酸在体外对妊娠期糖尿病孕妇及其新生儿的T细胞功能的影响

Background The aim of this investigation was to determine the in vitro effects of linseed, olive and Nigel oils on T cell proliferation and function in gestational diabetes. Methods Blood samples were collected from 40 control healthy and 32 gestational diabetic mothers and their newborns. Peripheral blood lymphocytes were isolated using a density gradient of Ficoll. T cell proliferation, interleukin-2 and -4 (IL-2, IL-4) secretion, fatty acid composition and intracellular oxidative status were investigated. Results Mitogen (Concanavalin A) stimulated lymphocyte proliferation, IL-2 secretion, intracellular reduced glutathione levels, superoxide dismutase (SOD) and catalase activities were l…

Desaturase expression in human cells: A new biomarker for fatty acid status?

In the present issue of the journal, J. E. Slagsvold, K. Thorstensen, M. Kvitland, M. Mack and K. S. Bjerve 1 investigate whether supply of essential fatty acids can regulate the expression of fatt...

The metabolic cascade leading to eicosanoid precursors--desaturases, elongases, and phospholipases A2--is altered in Zucker fatty rats.

Abstract Metabolic syndrome characterized by insulin resistance and obesity is accompanied by severe lipid metabolism perturbations and chronic low-grade inflammation. However, many unresolved questions remained regarding the regulation that underlie dyslipidemia, particularly the regulation of the metabolic cascade (synthesis and release) leading to eicosanoid precursors release. This study was undertaken to investigate the regulation of desaturases/elongases and phospholipases A2 during the establishment of metabolic syndrome. Our results showed that delta-6 desaturase as well as elongase-6 expressions were upregulated in 3-month-old Zucker fatty rats as compared to lean littermates, inde…

Oxidant and antioxidant status in mothers and their newborns according to birthweight

The aim of this study is to determine the oxidant and antioxidant status in Algerian mothers and their newborns according to birth weight.Subjects for the study were consecutively recruited from Tlemcen hospital. 139 pregnant women and their newborns were included. The plasma total antioxidant activity (ORAC), vitamins A, C, E, hydroperoxides, carbonyl proteins, and erythrocyte antioxidant enzyme activities (catalase, glutathione peroxidase, glutathione reductase and superoxide dismutase) were measured on mothers and their newborns. Lipid and lipoprotein parameters were also determined. The results were assessed in accordance with small for gestational age (SGA), appropriate (AGA) and large…

Recent advances on stearoyl-Coa desaturase regulation in fatty liver diseases.

Stearoyl-CoA desaturase 1 (SCD-1) is a delta-9 fatty acid desaturase that catalyzes the synthesis of monounsaturated fatty acids. Indeed, SCD-1 is the critical control point regulating hepatic lipogenesis and lipid oxidation. Due to its central role in lipid metabolism in the liver, recent studies have focused on the involvement of SCD-1 in the development of fatty liver during obesity, diabetes mellitus, hypertension, excessive alcohol consumption, and in subjects with high triglyceride blood concentrations. The accumulation of fat in liver cells can be a sign that harmful conditions are developing, possibly associated with or leading to inflammation of the liver. This review evaluates the…

Effect of ethanol on polyunsaturated fatty acid biosynthesis in hepatocytes from spontaneously hypertensive rats.

Background: Polyunsaturated fatty acids (PUFA) play a major role in membrane structures that are modified during alcoholism. PUFA are also precursors of second messengers—eicosanoids—involved in the regulation of blood pressure. Alcohol has been related to hypertension and to alterations in liver PUFA metabolism. We investigated the effects of ethanol on PUFA biogenesis in hepatocytes of Wistar Kyoto (WKY) rats and Spontaneously Hypertensive Rats (SHR). The effects of a diet enriched with n-3 PUFA, which is known to modulate hypertension, were also studied. Methods: Isolated hepatocytes from male normotensive Wistar Kyoto (WKY) rats and SHR were incubated for 60 min in the presence of label…