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…

Liver carbohydrate and lipid metabolism of insulin-deficient mice is altered by trans-10, cis-12 conjugated linoleic acid.

Feeding mice the trans-10, cis-12 (t10c12) conjugated linoleic acid (CLA) isomer is associated with lipodystrophy, insulin resistance, hyperinsulinemia, and liver steatosis. It has been hypothesized that CLA-induced liver steatosis is the result of increased hepatic lipogenesis stimulated by high insulin levels. We studied the effects of a 12-d t10c12CLA treatment (1 g/100 g diet) on liver carbohydrate and lipid metabolism in control and streptozotocin (STZ)-injected mice. STZ mice were characterized by insulin deficiency, hypertriglyceridemia, and depletion of liver triglyceride and glycogen. Remarkably, feeding t10c12CLA to diabetic mice (STZ-CLA) normalized these variables. Reconstitutio…

Reciprocal Enzymatic Interference of Carnitine Palmitoyltransferase I and Glycerol-3-Phosphate Acyltransferase in Purified Liver Mitochondria

(i) Highly purified mitochondrial fractions were practically devoid of microsomal contamination and of acyl-CoA ligase activity. (ii) In mitochondria, glycerol-3-phosphate acyltransferase (GPAT) activity was supported by two enzymes, the first being very active at low palmitoyl-CoA / albumin ratios and sensitive to external agents (external form), the second being detected only at higher palmitoyl-CoA / albumin ratios and insensitive to external agents (internal form). (iii) Carnitine palmitoyltransferase I (CPT I) activity was shown to inhibit external GPAT activity only. (iv) Glycerol-3-phosphate exerted an inhibitory effect on CPT I, even when GPAT was inactive. Reciprocal interaction of…

Activation of adipose tissue cannabinoid receptors 1 (CB1R) alters antilipolytic action of insulin and increases lipolysis in mice

Acute activation of cannabinoid receptors by anandamide reduces gastrointestinal motility and improves postprandial glycemia in mice.

International audience; The endocannabinoid system (ECS) is associated with an alteration of glucose homeostasis dependent on cannabinoid receptor-1 (CB1R) activation. However, very little information is available concerning the consequences of ECS activation on intestinal glucose absorption. Mice were injected intraperitoneally with anandamide, an endocannabinoid binding both CB1R and CB2R. We measured plasma glucose and xylose appearance after oral loading, gastrointestinal motility, and glucose transepithelial transport using the everted sac method. Anandamide improved hyperglycemia after oral glucose charge whereas glucose clearance and insulin sensitivity were impaired, pointing out so…

Upregulation of liver VLDL receptor and FAT/CD36 expressions in LDLR-/- apoB100/100 mice fed trans-10,cis-12 conjugated linoleic acid

International audience; This study explores the mechanisms responsible for the fatty liver setup in mice fed trans-10,cis-12 conjugated linoleic acid (t10c12 CLA), hypothesizing that an induction of low density lipoprotein receptor (LDLR) expression is associated with lipid accumulation. To this end, the effects of t10c12 CLA treatment on lipid parameters, serum lipoproteins, and expression of liver lipid receptors were measured in LDLR(-/-) apoB(100/100) mice as a model of human familial hypercholesterolemia itself depleted of LDLR. Mice were fed t10c12 CLA over 2 or 4 weeks. We first observed that the treatment induced liver steatosis, even in the absence of LDLR. Mice treated for 2 weeks…

Distribution of Δ5-olefinic acids in the triacylglycerols fromPinus koraiensisandPinus pinasterseed oils

Purified triacylglycerols (TAG) fromPinus koraiensis andP. pinaster seed oils, which are interesting and commercially available sources of Δ5-olefinic acids (i.e.,cis-5,cis-9,cis-12 18:3 andcis-5,cis-11,cis-14 20:3 acids) were fractionated by reversed-phase high-performance liquid chromatography, and each fraction was examined by capillary gas-liquid chromatography for its fatty acid composition. A structure could be assigned to more than 92% of TAG from both oils. In both instances, ca. 48% of the TAG were shown to contain at least one δ5-olefinic acid. In the great majority of TAG, our data showed that there is only one molecule of δ5-olefinic acid per molecule of TAG. This is compatible …

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…

Influence of phytosterols on the structural and dynamic properties of plant plasma membrane

National audience; The complex mixture of sterols, namely phytosterols, found in the plasma membrane (PM) of plant cells is an intriguing characteristic. In the present work, we characterized the sterol composition of tobacco BY-2 cell PM, and we adapted a sterol manipulation method to this plant material. Methyl-b-cyclodextrin was found to induce a drastic reduction of the PM total free sterol content, with a low specificity for the different phytosterols, and without effect on steryl-conjugates. The consequences of phytosterols depletion were investigated by means of fluorescence spectroscopy and biochemical detergent resistant membrane (DRM) fraction purification methods. Data obtained w…

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

Association of liver steatosis with lipid oversecretion and hypotriglyceridaemia in C57BL/6j mice fed trans-10, cis-12-linoleic acid

AbstractConjugated linoleic acids (CLA) have recently been recognized to reduce body fat and plasma lipids in some animals. This study demonstrated that the steatosis accompanying the fat loss induced by trans-10,cis-12-C18:2 (CLA2) and not cis-9,trans-11-C18:2 (CLA1) isomer in C57BL/6j mice was not due to an alteration of the liver lipoprotein production that was even increased. The 3-fold decrease in plasma triacylglycerol contents and the induction of mRNA expression of low-density lipoprotein receptors concomitantly observed in CLA2-fed mice suggested an increase in the lipoprotein clearance at the level of the liver itself. CLA1 feeding produced similar but attenuated effects on trigly…

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…

A role for the peroxisomal 3-ketoacyl-CoA thiolase B enzyme in the control of PPARα-mediated upregulation of SREBP-2 target genes in the liver.: ThB and cholesterol biosynthesis in the liver

International audience; Peroxisomal 3-ketoacyl-CoA thiolase B (Thb) catalyzes the final step in the peroxisomal β-oxidation of straight-chain acyl-CoAs and is under the transcription control of the nuclear hormone receptor PPARα. PPARα binds to and is activated by the synthetic compound Wy14,643 (Wy). Here, we show that the magnitude of Wy-mediated induction of peroxisomal β-oxidation of radiolabeled (1-(14)C) palmitate was significantly reduced in mice deficient for Thb. In contrast, mitochondrial β-oxidation was unaltered in Thb(-/-) mice. Given that Wy-treatment induced Acox1 and MFP-1/-2 activity at a similar level in both genotypes, we concluded that the thiolase step alone was respons…

Conjugated linoleic acid isomers in mitochondria

The beneficial effects exerted by low amounts of conjugated linoleic acids (C222222237) suggest that CLA are maximally conserved and raise the question about their mitochondrial oxidizability. Cis-9,trans-11-C18:2 (CLA1) and trans-10,cis-12-C18:2 (CLA2) were compared to cis-9,cis-12-C18:2 (linoleic acid; LA) and cis-9-C16:1 (palmitoleic acid; PA), as substrates for total fatty acid (FA) oxidation and for the enzymatic steps required for the entry of FA into rat liver mitochondria. Oxygen consumption rate was lowest when CLA1 was used as a substrate with that on CLA2 being intermediate between it and the respiration on LA and PA. The order of the radiolabeled FA oxidation rate was PA >> LA >…

Mitochondrial respiration on rumenic and linoleic acids

Rumenic acid ( cis -9, trans -11-C 18:2 ) represents approx. 80% of conjugated linoleic acid (CLA) in dairy products. CLA has been shown to exert beneficial effects on health, but little work has been devoted to the ability to oxidize CLA isomers and the role of these isomers in the modulation of β-oxidation flux. In the present study, respiration on rumenic acid was compared with that on linoleic acid ( cis -9, cis -12-C 18:2 ) with the use of rat liver mitochondria. In state-3, respiration was decreased by half with rumenic acid in comparison with linoleic acid. In the uncoupled state, respiration on CLA remained 30% lower. The lower ability to oxidize CLA was investigated through charact…

EFFECTS OF CYCLOPROPENOID FATTY ACIDS (BAOBAB SEED OIL) ON THE FATTY ACID PROFILE OF LIPIDS FROM DIFFERENT TISSUES IN THE RAT

Rats were fed for 8 weeks a diet containing either Baobab seed oil (FBO) rich in cyclopropenoid fatty acids (CPFA) or heated oil (HBO) devoid of CPFA. In FBO rats, compared to controls (CO), the monounsaturated fatty acid content of adipose tissue lipids, liver triacylglycerols, liver and adrenal cholesteryl esters and liver, kidney, adrenal phospholipids were highly decreased to the benefit of saturated fatty acid content. In cholesteryl esters and phospholipids, the arachidonic acid (20:4 n-6) content was markedly decreased, especially in adrenals. In adrenal cholesteryl esters, adrenic acid (22:4 n-6) content was decreased more than its precursor. The effects of HBO on the tissue lipid f…

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…

Modulation of the hepatic fatty acid pool in peroxisomal 3-ketoacyl-CoA thiolase B-null mice exposed to the selective PPARalpha agonist Wy14,643

10 pages; International audience; The peroxisomal 3-ketoacyl-CoA thiolase B (Thb) gene was previously identified as a direct target gene of PPARalpha, a nuclear hormone receptor activated by hypolipidemic fibrate drugs. To better understand the role of ThB in hepatic lipid metabolism in mice, Sv129 wild-type and Thb null mice were fed or not the selective PPARalpha agonist Wy14,643 (Wy). Here, it is shown that in contrast to some other mouse models deficient for peroxisomal enzymes, the hepatic PPARalpha signaling cascade in Thb null mice was normal under regular conditions. It is of interest that the hypotriglyceridemic action of Wy was reduced in Thb null mice underlining the conclusion t…

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…

Moderate consumption of beer reduces liver triglycerides and aortic cholesterol deposit in LDLr-/- apoB100/100 mice.

This study was designed to address the effects of a moderate consumption of beer on serum and liver lipid parameters and on the development of aortic lesions in a mouse model associated with a human atherogenic lipoprotein profile. LDLr(-/-) apoB(100/100) mice received each day during 12 weeks either water, mild beer (0.570g of ethanol/kg of body weight) or ethanol-free beer in a single pure dose. Serum and liver lipid parameters were analyzed and atherosclerotic lesions were estimated in heart and aorta through their total cholesterol content. mRNA levels of enzymes and receptors involved in lipoprotein uptake, in fatty acid esterification and oxidation, and in reverse cholesterol transpor…

Effect of dietary n−3 and n−6 polyunsaturated fatty acids on lipid-metabolizing enzymes in obese rat liver

This study was designed to examine whether n-3 and n-6 polyunsaturated fatty acids at a very low dietary level (about 0.2%) would alter liver activities in respect to fatty acid oxidation. Obese Zucker rats were used because of their low level of fatty acid oxidation, which would make increases easier to detect. Zucker rats were fed diets containing different oil mixtures (5%, w/w) with the same ratio of n-6/n-3 fatty acids supplied either as fish oil or arachidonic acid concentrate. Decreased hepatic triacylglycerol levels were observed only with the diet containing fish oil. In mitochondrial outer membranes, which support carnitine palmitoyltransferase I activity, cholesterol content was …

Fatty acid oxidation and related gene expression in heart depleted of carnitine by mildronate treatment in the rat.

The metabolic and genic effects induced by a 20-fold lowering of carnitine content in the heart were studied in mildronate-treated rats. In the perfused heart, the proportion of palmitate taken up then oxidized was 5-10% lower, while the triacylglycerol (TAG) formation was 100% greater than in controls. The treatment was shown to increase the maximal capacity of heart homogenates to oxidize palmitate, the mRNA level of carnitine palmitoyltransferase I (CPT-I) isoforms, the specific activity of CPT-I in subsarcolemmal mitochondria and the total carnitine content of isolated mitochondria. Concomitantly, the increased mRNA expression of lipoprotein lipase, fatty acid translocase and enzymes of…

Identification de nouveaux antagonistes des récepteurs aux endocannabinoïdes à action périphérique susceptibles d'améliorer les paramètres glucido-lipidiques chez la souris obèse

Identification de nouveaux antagonistes des récepteurs aux endocannabinoïdes à action périphérique susceptibles d'améliorer les paramètres glucido-lipidiques chez la souris obèse. 30. réunion de l’association française d’étude et de recherche sur l’Obésite (AFERO)

Determination of heavy metal content and lipid profiles in mussel extracts from two sites on the moroccan atlantic coast and evaluation of their biological activities on MIN6 pancreatic cells

Mussels may concentrate pollutants, with possibly significant side effects on human health. Therefore, mussels (Mytilus galloprovincialis) from two sites of the Moroccan Atlantic coast (Jorf Lasfar [JL], an industrial site, and Oualidia [OL], a vegetable-growing area), were subjected to biochemical analyses to quantify the presence of heavy metals (Cd, Cr, and Pb) and to establish the lipid profile: fatty acid, cholesterol, oxysterol, phytosterol and phospholipid content. In addition, mussel lipid extracts known to accumulate numerous toxic components were tested on murine pancreatic β-cells (MIN6), and their biological activities were measured with various flow cytometric and biochemical m…

Hypolipidaemic effects of fenofibrate are not altered by mildronate-mediated normalization of carnitine concentration in rat liver.

The five-fold higher carnitine content in the liver of fenofibrate-treated rats addresses the question about the possible role of this enhancement in the hypolipidaemic effect of the drug and the underlying mechanisms. When fenofibrate was administered with mildronate (a gamma-butyrobetaine hydroxylase inhibitor) in suitable amount, the content in carnitine was found to be normalized in liver. However, triglyceride contents of liver and serum were then at least as low as in rats treated by fenofibrate only. When carnitine concentration was lowered by mildronate to the third of the normal value, a marked increase in triglycerides occurred both in liver and serum, while the five-fold increase…

Microscale synthesis of phosphatidyl-[3H]choline from 1,2-diacylglycerol. Assessment of isomerization by reversed-phase high-performance liquid chromatography

The synthesis of rac-1-palmitoyl-2-oleoylglycero-3-phospho-[3H]choline of high specific activity was carried out on a microscale by making 7 mumol of rac-1-palmitoyl-2-oleoylglycerol react first with an equimolar amount of POCl3 and then of [3H]choline. After purification by thin-layer chromatography and normal-phase high-performance liquid chromatography and normal-phase high-performance liquid chromatography (HPLC), the yield of the synthesis of [3H]phosphatidylcholine (120 microCi/mumol) was 22%. rac-1-Palmitoyl-2-oleoylglycerol was purified before use by reversed-phase HPLC under conditions which were nonisomerizing and allowed the separation of 1,2- and 1,3-isomers of diacylglycerol. E…

Different effects of pioglitazone and rosiglitazone on lipid metabolism in mouse cultured liver explants.

Background Pioglitazone (PIO) and rosiglitazone (ROSI) are widely used as oral antidiabetic agents for treatment of type 2 diabetes. Although these medications exert similar effects on blood glucose, recent clinical studies indicated that PIO has a more pronounced beneficial effect on lipid parameters than ROSI. In order to get further insight into the lipid effects of both drugs, we tested whether PIO, compared to ROSI, could exert direct effects on lipid liver metabolism in relation with plasma lipids. Methods We performed in vitro studies using mice liver slices incubated 21 h either with ROSI (1 µmol/L) or PIO (7.5 µmol/L). Results We showed that both glitazones slightly reduced HMG-CoA…

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…

Hepatic steatosis is not due to impaired fatty acid oxidation capacities in C57BL/6J mice fed the conjugated trans-10,cis-12-isomer of linoleic acid.

Decreased body fat mass and liver steatosis have been reported in mice fed diets containing the conjugated linoleic acid trans-10,cis-12-C18:2 (CLA2), but not in those fed diets containing cis-9,trans-11-C18:2 (CLA1). Because the decrease in fatty acid (FA) oxidation may cause fat accumulation, we questioned whether the effects of both CLAs on enzyme activities and mRNA expression were related to liver FA oxidation. To address this question, 7-wk-old male C57BL/6J mice were fed for 4 wk a diet supplemented with 1% CLA1, CLA2, or cis-9-C18:1 (control) esterified as triacylglycerols. In CLA2-fed mice, the proportions of CLA2 in the total FA of liver lipids were substantially lower than those …

Changes in membrane lipid composition in ethanol- and acid-adapted Oenococcus oeni cells: characterization of the cfa gene by heterologous complementation

International audience; Cyclopropane fatty acid (CFA) synthesis was investigated in Oenococcus oeni. The data obtained demonstrated that acid-grown cells or cells harvested in the stationary growth phase showed changes in fatty acid composition similar to those of ethanol-grown cells. An increase of the CFA content and a decrease of the oleic acid content were observed. The biosynthesis of CFAs from unsaturated fatty acid phospholipids is catalysed by CFA synthases. Quantitative real-time-PCR experiments were performed on the cfa gene of O. oeni, which encodes a putative CFA synthase. The level of cfa transcripts increased when cells were harvested in stationary phase and when cells were gr…

Involvement of microsomal vesicles in part of the sensitivity of carnitine palmitoyltransferase I to malonyl-CoA inhibition in mitochondrial fractions of rat liver.

Liver mitochondrial fractions as normally isolated contain only 10-20% of total mitochondria and may not be representative of the whole mitochondrial population. This study was designed to evaluate the dependence of the sensitivity of carnitine palmitoyl-transferase I (CPT I) to malonyl-CoA inhibition in mitochondrial fractions that are not normally studied. Four fractions prepared from rat liver were found to be contaminated to different extents by microsome vesicles, on the basis of marker-enzyme activities and micrographic data. Purification of mitochondrial fractions on a Percoll gradient decreased to some extent the microsomal contamination, which was due in part to the existence of cl…

Overactivation of the endocannabinoid system alters the antilipolytic action of insulin in mouse adipose tissue.

Evidence has accumulated that obesity-related metabolic dysregulation is associated with overactivation of the endocannabinoid system (ECS), which involves cannabinoid receptor 1 (CB1R), in peripheral tissues, including adipose tissue (AT). The functional consequences of CB1R activation on AT metabolism remain unclear. Since excess fat mobilization is considered an important primary event contributing to the onset of insulin resistance, we combined in vivo and in vitro experiments to investigate whether activation of ECS could alter the lipolytic rate. For this purpose, the appearance of plasma glycerol was measured in wild-type and CB1R−/− mice after acute anandamide administration or inh…

Enhancement of activities relative to fatty acid oxidation in the liver of rats depleted of l-carnitine by d-carnitine and a γ-butyrobetaine hydroxylase inhibitor

Abstract This study was designed to examine whether the depletion of l -carnitine may induce compensatory mechanisms allowing higher fatty acid oxidative activities in liver, particularly with regard to mitochondrial carnitine palmitoyltransferase I activity and peroxisomal fatty acid oxidation. Wistar rats received d -carnitine for 2 days and 3-(2,2,2-trimethylhydrazinium)propionate (mildronate), a non-competitive inhibitor of γ-butyrobetaine hydroxylase, for 10 days. They were starved for 20 hr before being sacrificed. A dramatic reduction in carnitine concentration was observed in heart, skeletal muscles and kidneys, and to a lesser extent, in liver. Triacylglycerol content was found to …

Early Low-Fat Diet Enriched With Linolenic Acid Reduces Liver Endocannabinoid Tone and Improves Late Glycemic Control After a High-Fat Diet Challenge in Mice.

International audience; Evidence suggests that alterations of glucose and lipid homeostasis induced by obesity are associated with the elevation of endocannabinoid tone. The biosynthesis of the two main endocannabinoids, N-arachidonoylethanolamine and 2-arachidonoyl-glycerol, which derive from arachidonic acid, is influenced by dietary fatty acids (FAs). We investigated whether exposure to n-3 FA at a young age may decrease tissue endocannabinoid levels and prevent metabolic disorders induced by a later high-fat diet (HFD) challenge. Three-week-old mice received a 5% lipid diet containing lard, lard plus safflower oil, or lard plus linseed oil for 10 weeks. Then, mice were challenged with a…

Effects of dietary treatment of rats with eicosapentaenoic acid or docosahexaenoic acid on hepatic lipid metabolism

(1) Effects of dietary treatment of male albino rats with eicosapentaenoic acid (EPA) or docosahexaenoic acid on hepatic mitochondrial lipid metabolism have been investigated. (2) Mitochondria isolated from rats given these treatments were shown to have increased ability to respire on acyl-CoA esters in the presence of malonate. This effect was expressed with most of the long-chain acyl-CoA esters used as substrates. When malonate in the incubations was replaced with malate, mitochondria from treated animals were found to exhibit diminished rates of respiration on polyunsaturated acyl-CoA esters, in particular linolenoyl-, eicosapentaenoyl- and docosahexaenoyl-CoA. This phenomenon could not…

Regulation of lipid flux between liver and adipose tissue during transient hepatic steatosis in carnitine-depleted rats

Rats with carnitine deficiency due to trimethylhydrazinium propionate (mildronate) administered at 80 mg/100 g body weight per day for 10 days developed liver steatosis only upon fasting. This study aimed to determine whether the transient steatosis resulted from triglyceride accumulation due to the amount of fatty acids preserved through impaired fatty acid oxidation and/or from up-regulation of lipid exchange between liver and adipose tissue. In liver, mildronate decreased the carnitine content by approximately 13-fold and, in fasted rats, lowered the palmitate oxidation rate by 50% in the perfused organ, increased 9-fold the triglyceride content, and doubled the hepatic very low density …

Vaccenic and elaidic acid equally esterify into triacylglycerols, but differently into phospholipids of fed rat liver cells.

Elaidic acid (trans-9-C18:1 or trans-9) is assumed to exert atherogenic effects due to its double bond configuration. The possibility that trans-9 and vaccenic acid (trans-11-C18:1 or trans-11), its positional isomer, were biochemically equivalent and interchangeable compounds, was investigated by reference to their cis-isomers through esterification-related activities using rat liver cells and subcellular fractions. In hepatocytes, both trans-C18:1 were incorporated to the same extent in triacylglycerols, but trans-9 was more esterified than trans-11 into phospholipids (P < 0.05). Glycerol-3-phosphate acyltransferase activity in microsomes was lower with trans-11 than with trans-9, while t…

O45 L’activation des récepteurs aux endocannabinoïdes CB1R du tissu adipeux inhibe l’action anti-lipolytique de l’insuline

Introduction Il est maintenant bien etabli que l’obesite est associee a une suractivation du systeme endocannabinoide (SEC). Des travaux recents suggerent que le blocage des recepteurs aux endocannabinoides 1 (CB1R) peripheriques conduit a une amelioration du metabolisme glucidique et lipidique independamment des effets centraux modulant la prise alimentaire. Le role du SEC dans le tissu adipeux etant encore mal defini, cette etude vise a preciser les consequences de l’activation des CB1R sur la lipolyse. Materiels et methodes Les effets de l’anandamide (endocannabinoide) sur l’activite lipolytique estimee par la production de glycerol plasmatique ont ete testes chez la souris in vivo apres…

Modulation of peroxisomes abundance by argan oil and lipopolysaccharides in acyl-CoA oxidase 1-deficient fibroblasts

Pseudo-neonatal adrenoleukodystrophy (P-NALD) is a neurodegenerative disorder caused by acyl-CoA oxidase 1 (ACOX1) deficiency with subsequent impairment of peroxisomal fatty acid β-oxidation, accumulation of very long chain fatty acids (VLCFAs) and strong reduction in peroxisome abundance. Increase in peroxisome number has been previously suggested to improve peroxisomal disorders, and in this perspective, the present work was aimed at exploring whether modulation of peroxisomes abundance could be achieved in P-NALD fibroblasts. Here we showed that treatment with the natural Argan oil induced peroxisome proliferation in P-NALD fibroblasts. This induction was independent on activations of bo…

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 …

Polyunsaturated n-3 and n-6 fatty acids at a low level in the diet alter mitochondrial outer membrane parameters in Wistar rat liver

Abstract This study was designed to examine whether n-3 and n-6 polyunsaturated fatty acids (PUFA) at a very low level in the diet (about 0.2%) may alter the fatty acid composition of mitochondrial outer membranes and the characteristics of carnitine palmitoyltransferase I (CPTI) activity in the liver of normal Wistar rats. The animals were fed diets containing different oil mixtures (5% wt/wt) with the same ratio of n-6 n-3 fatty acids supplied either as fish oil or arachidonic acid concentrate. The cholesterol content of the mitochondrial outer membranes from liver was similar for all diets, while the percentage of 22:6n-3 and 20:4n-6 in phospholipids was enhanced with the diets containin…

P259 Identification de nouveaux antagonistes des récepteurs aux endocannabinoïdes à action périphérique susceptibles d’améliorer les paramètres glucido-lipidiques chez la souris obèse

Introduction Le systeme endocannabinoide (SEC) est une cible therapeutique potentielle pour lutter contre l’obesite. Ainsi, le Rimonabant®, un antagoniste des recepteurs aux endocannabinoides 1 (CB1R) diminue la masse corporelle et ameliore les parametres glucido-lipidiques de patients obeses. Neanmoins, ce medicament a ete retire du marche suite a des effets centraux induisant des troubles neuropsychiatriques. L’objectif de cette etude est d’identifier des analogues du Rimonabant® a action peripherique susceptibles d’avoir des effets benefiques sur le metabolisme glucido-lipidique de la souris. Materiels et methodes Des analogues du Rimonabant® ne passant pas la barriere hemato-encephaliqu…

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…

Disturbances in cholesterol, bile acid and glucose metabolism in peroxisomal 3-ketoacylCoA thiolase B deficient mice fed diets containing high or low saturated fat contents.

SPE IPM UB; International audience; : The peroxisomal 3-ketoacyl-CoA thiolase B (ThB) catalyzes the thiolytic cleavage of straight chain 3-ketoacyl-CoAs. Up to now, the ability of ThB to interfere with lipid metabolism was studied in mice fed a routinely laboratory chow enriched or not with the synthetic agonist Wy14,643, a pharmacological activator of the nuclear hormone receptor PPARα. The aim of the present study was therefore to determine whether ThB could play a role in obesity and lipid metabolism when mice are chronically fed a synthetic High Fat Diet (HFD) or a Low Fat Diet (LFD) as a control diet. To investigate this possibility, wild-type (WT) mice and mice deficient for Thb (Thb(…