Liver Phospholipids Research Articles

Dietary fatty acids modulate liver mitochondrial cardiolipin content and its fatty acid composition in rats with non alcoholic fatty liver disease

No data are reported on changes in mitochondrial membrane phospholipids in non-alcoholic fatty liver disease. We determined the content of mitochondrial membrane phospholipids from rats with non alcoholic liver steatosis, with a particular attention for cardiolipin (CL) content and its fatty acid composition, and their relation with the activity of the mitochondrial respiratory chain complexes. Different dietary fatty acid patterns leading to steatosis were explored. With high-fat diet, moderate macrosteatosis was observed and the liver mitochondrial phospholipid class distribution and CL fatty acids composition were modified. Indeed, both CL content and its C18:2n-6 content were increased with liver steatosis. Moreover, mitochondrial ATP synthase activity was positively correlated to the total CL content in liver phospholipid and to CL C18:2n-6 content while other complexes activity were negatively correlated to total CL content and/or CL C18:2n-6 content of liver mitochondria. The lard-rich diet increased liver CL synthase gene expression while the fish oil-rich diet increased the (n-3) polyunsaturated fatty acids content in CL. Thus, the diet may be a significant determinant of both the phospholipid class content and the fatty acid composition of liver mitochondrial membrane, and the activities of some of the respiratory chain complex enzymes may be influenced by dietary lipid amount in particular via modification of the CL content and fatty acid composition in phospholipid.

Liver phospholipid transfer protein (PLTP) expression with a PLTP-null background promotes very low-density lipoprotein production in mice

It is known that plasma phospholipid transfer protein (PLTP) activity influences lipoprotein metabolism. The liver is one of the major sites of lipoprotein production and degradation, as well as of PLTP expression. To address the impact of liver-expressed PLTP on lipoprotein metabolism, we created a mouse model that expresses PLTP in the liver acutely and specifically, with a PLTP-null background. This approach in mouse model preparations can also be used universally for evaluating the function of many other genes in the liver. We found that liver PLTP expression dramatically increases plasma levels of non-high-density lipoprotein (HDL) cholesterol (2.7-fold, P < 0.0001), non-HDL phospholipid (2.5-fold, P < 0.001), and triglyceride (51%, P < 0.01), but has no significant influence on plasma HDL lipids compared with controls. Plasma apolipoprotein (apo)B levels were also significantly increased in PLTP-expressing mice (2.2-fold, P < 0.001), but those of apoA-I were not. To explore the mechanism involved, we examined the lipidation and secretion of nascent very low-density lipoprotein (VLDL), finding that liver PLTP expression significantly increases VLDL lipidation in hepatocyte microsomal lumina, and also VLDL secretion into the plasma. It is possible to prepare a mouse model that expresses the gene of interest only in the liver, but not in other tissues. Our results suggest, for the first time, that the major function of liver PLTP is to drive VLDL production and makes a small contribution to plasma PLTP activity.

Menhaden oil, but not safflower or soybean oil, aids in restoring the polyunsaturated fatty acid profile in the novel delta-6-desaturase null mouse

BackgroundPolyunsaturated fatty acids (PUFA) have diverse biological effects, from promoting inflammation to preventing cancer and heart disease. Growing evidence suggests that individual PUFA may have independent effects in health and disease. The individual roles of the two essential PUFA, linoleic acid (LA) and α-linolenic acid (ALA), have been difficult to discern from the actions of their highly unsaturated fatty acid (HUFA) downstream metabolites. This issue has recently been addressed through the development of the Δ-6 desaturase knock out (D6KO) mouse, which lacks the rate limiting Δ-6 desaturase enzyme and therefore cannot metabolize LA or ALA. However, a potential confounder in this model is the production of novel Δ-5 desaturase (D5D) derived fatty acids when D6KO mice are fed diets containing LA and ALA, but void of arachidonic acid.ObjectiveThe aim of the present study was to characterize how the D6KO model differentially responds to diets containing the essential n-6 and n-3 PUFA, and whether the direct provision of downstream HUFA can rescue the phenotype and prevent the production of D5D fatty acids.MethodologyLiver and serum phospholipid (PL) fatty acid composition was examined in D6KO and wild type mice fed i) 10% safflower oil diet (SF, LA rich) ii) 10% soy diet (SO, LA+ALA) or iii) 3% menhaden oil +7% SF diet (MD, HUFA rich) for 28 days (n = 3-7/group).ResultsNovel D5D fatty acids were found in liver PL of D6KO fed SF or SO-fed mice, but differed in the type of D5D fatty acid depending on diet. Conversely, MD-fed D6KO mice had a liver PL fatty acid profile similar to wild-type mice.ConclusionsThrough careful consideration of the dietary fatty acid composition, and especially the HUFA content in order to prevent the synthesis of D5D fatty acids, the D6KO model has the potential to elucidate the independent biological and health effects of the parent n-6 and n-3 fatty acids, LA and ALA.

Correlations between blood and tissue omega-3 LCPUFA status following dietary ALA intervention in rats

The aim of this study was to assess relationships between the fatty acid contents of plasma and erythrocyte phospholipids and those in liver, heart, brain, kidney and quadriceps muscle in rats. To obtain a wide range of tissue omega-3 (n-3) long chain polyunsaturated fatty acids (LCPUFA) we subjected weanling rats to dietary treatment with the n-3 LCPUFA precursor, alpha linolenic acid (ALA, 18:3 n-3) for 3 weeks. With the exception of the brain, we found strong and consistent correlations between the total n-3 LCPUFA fatty acid content of both plasma and erythrocyte phospholipids with fatty acid levels in all tissues. The relationships between eicosapentaenoic acid (EPA, 20:5 n-3) and docosapentaenoic acid (DPA, 22:5 n-3) content in both blood fractions with levels in liver, kidney, heart and quadriceps muscle phospholipids were stronger than those for docosahexaenoic acid (DHA, 22:6 n-3). The strong correlations between the EPA+DHA (the Omega-3 Index), total n-3 LCPUFA and total n-3 PUFA contents in both plasma and erythrocyte phospholipids and tissues investigated in this study suggest that, under a wide range of n-3 LCPUFA values, plasma and erythrocyte n-3 fatty acid content reflect not only dietary PUFA intakes but also accumulation of endogenously synthesised n-3 LCPUFA, and thus can be used as a reliable surrogate for assessing n-3 status in key peripheral tissues.

Effects of recombinant human keratinocyte growth factor on surfactant, plasma, and liver phospholipid homeostasis in hyperoxic neonatal rats

Respiratory distress and bronchopulmonary dysplasia (BPD) are major problems in preterm infants that are often addressed by glucocorticoid treatment and increased oxygen supply, causing catabolic and injurious side effects. Recombinant human keratinocyte growth factor (rhKGF) is noncatabolic and antiapoptotic and increases surfactant pools in immature lungs. Despite its usefulness in injured neonatal lungs, the mechanisms of improved surfactant homeostasis in vivo and systemic effects on lipid homeostasis are unknown. We therefore exposed newborn rats to 85% vs. 21% oxygen and treated them systemically with rhKGF for 48 h before death at 7 days. We determined type II pneumocyte (PN-II) proliferation, surfactant protein (SP) mRNA expression, and the pulmonary metabolism of individual phosphatidylcholine (PC) species using [D(9)-methyl]choline and tandem mass spectrometry. In addition, we assessed liver and plasma lipid metabolism, addressing PC synthesis de novo, the liver-specific phosphatidylethanolamine methyl transferase (PEMT) pathway, and triglyceride concentrations. rhKGF was found to maintain PN-II proliferation and increased SP-B/C expression and surfactant PC in both normoxic and hyperoxic lungs. We found increased total PC together with decreased [D(9)-methyl]choline enrichment, suggesting decreased turnover rather than increased secretion and synthesis as the underlying mechanism. In the liver, rhKGF increased PC synthesis, both de novo and via PEMT, underlining the organotypic differences of rhKGF actions on lipid metabolism. rhKGF increased the hepatic secretion of newly synthesized polyunsaturated PC, indicating improved systemic supply with choline and essential fatty acids. We suggest that rhKGF has potential as a therapeutic agent in neonates by improving pulmonary and systemic PC homeostasis.

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.

Changes in tissue and mitochondrial membrane composition during rapid growth, maturation and aging in rainbow trout, Oncorhynchus mykiss

Membrane compositions, particularly of mitochondria, could be critical factors in the mechanisms of growth and aging processes, especially during phases of high oxidative stress that result in molecular damage. In the present study, liver and mitochondrial membrane phospholipid (PL) compositions were analyzed in rainbow trout during its four first years of life, a period characterized by rapid growth and high oxidative stress. Specifically, farmed fish of three ages (1-, 2- and 4-years) were studied, and PL compositions of whole liver and liver mitochondria, and fatty acid compositions of individual PL classes were determined. Liver mitochondrial membranes showed a PL composition different to that of the whole tissue suggesting adaptation of cell and subcellular membranes to specific functions. Individual PL had characteristic fatty acid compositions that were similar in whole liver and mitochondrial membranes. Whole liver and mitochondria showed increased lipid peroxidation with age along with changes in membrane PL fatty acid compositions. Most PL classes showed similar changes in fatty acid composition among the age groups, with reduced proportions of docosahexaenoic acid (DHA) and, generally, concomitantly increased levels of monounsaturated fatty acids, which together resulted in reduced peroxidation index (PIn). However, total polyunsaturated fatty acid (PUFA) content did not change significantly with age due to increased eicosapentaenoic acid, docosapentaenoic acid and, in most PL, increased n-6 PUFA. These results suggest there may be oxidation of PL DHA with compensatory mechanisms to maintain membrane fluidity and function. However, modification of fatty acid composition of specific PLs, such as cardiolipin, could affect the electron transport chain efficiency and propagate the oxidative reaction throughout the cell. In addition, both the content and fatty acid composition of sphingomyelin, which has been suggested as a possible mediator of cell dysfunction and apoptosis, changed with age differently to the other PL classes. Moreover, these changes showed different trends between mitochondria and whole liver. These data suggest there is marked oxidative stress associated with rapid growth and maturation in rainbow trout. Changes observed in membrane lipids point to their possible participation in the processes involved in this species response to oxidative stress and damage accumulation rate.

Interaction Between Marginal Zinc and High Fat Supply on Lipid Metabolism and Growth of Weanling Rats

The impact of a moderate Zn deficiency on growth and plasma and liver lipids was investigated in two 4-week experiments with male weanling rats fed fat-enriched diets. Semisynthetic, approximately isocaloric diets containing 3% soybean oil were supplemented with either 7 or 100 mg Zn/kg diet and with 22% beef tallow (BT) or sunflower oil (SF). In Experiment 1, which compared the dietary fat level and the fat source in a factorial design of treatments, all diets were fed ad libitum to 6 × 8 animals, whereas intake of the high-Zn BT and SF diets was restricted in Experiment 2 (5 × 6 rats) to the level of intake of the respective low-Zn diets. The low-Zn SF diet consistently depressed food intake and final live weights of the animals to a greater extent than the other low-Zn diets, while intake and growth were comparable among the animals fed the high-Zn diets. The marginal Zn deficit per se did not alter plasma triglyceride and cholesterol concentrations nor hepatic concentrations of triglyceride, cholesterol and phospholipids. The fatty acid pattern of liver phospholipids did not indicate that chain elongation and desaturation of fatty acids was impaired by a lack of zinc. It was concluded that dietary energy and fat intake, and fat source have a greater effect on plasma and liver lipids than a moderate Zn deficiency. Marginally Zn-deficient diets enriched with sunflower oil as a major energy source cause a greater growth retardation than diets rich in carbohydrates or beef tallow.

Arachidonic acid and docosahexaenoic acid supplemented to an essential fatty acid–deficient diet alters the response to endotoxin in rats

This study examined fatty acid profiles, triene-tetraene ratios (20:3n9/20:4n6), and nutritional and inflammatory markers in rats fed an essential fatty acid–deficient (EFAD) diet provided as 2% hydrogenated coconut oil (HCO) alone for 2 weeks or with 1.3 mg of arachidonic acid (AA) and 3.3 mg of docosahexaenoic acid (DHA) (AA + DHA) added to achieve 2% fat. Healthy controls were fed an AIN 93M diet (AIN) with 2% soybean oil. The HCO and AA + DHA diets led to significant reductions of linoleic acid, α-linolenic acid, and AA (20:4n6) and increases in Mead acid (20:3n9) in plasma and liver compared with the AIN diet; but the triene-tetraene levels remained well within normal. However, levels of 20:3n9 and 20:4n6 were lower in liver phospholipids in the AA + DHA than in HCO group, suggesting reduced elongation and desaturation in ω-9 and -6 pathways. The AA + DHA group also had significantly lower levels of 18:1n9 and 16:1n7 as well as 18:1n9/18:0 and 16:1n7/16:0 than the HCO group, suggesting inhibition of stearyl-Co A desaturase–1 activity. In response to lipopolysaccharide, the levels of tumor necrosis factor and interleukin-6 were significantly lower with HCO, reflecting reduced inflammation. The AA + DHA group had higher levels of IL-6 and C-reactive protein than the HCO group but significantly lower than the AIN group. However, in response to endotoxin, interleukin-6 was higher with AA + DHA than with AIN. Feeding an EFAD diet reduces baseline inflammation and inflammatory response to endotoxin long before the development of EFAD, and added AA + DHA modifies this response.

Fish oil supplementation improved liver phospholipids fatty acid composition and parameters of oxidative stress in male wistar rats

In the present study, we examined the effects of fish oil supplementation in 3 months old male Wistar rats on changes in plasma and liver lipid metabolism and oxidative stress parameters. Twenty Wistar rats were randomly divided into two groups of ten animals: control group and intervention group, treated for 6 weeks with fish oil capsules containing 45 mg eicosapentanoic acid and 30 mg docosahexanoic acid. After intervention, biochemical parameters in plasma [triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and total cholesterol, urea, creatinine and uric acid], fatty acid (FAs) profile of liver phospholipids and parameters of oxidative stress in liver [activity of catalase, superoxide dismutase and paraoxonase (PON1), concentration of nitrites, lipid peroxidation (LPO), free thiol (SH) groups and lactate dehydrogenase (LDH) izoenzymes were determined. Treatment with fish oil improved FAs profile of liver phospholipids, increasing n-3 FAs and decreasing n-6/n-3 ratio. Significant decrease in plasma TG and LDL concentration, and increase in the level of HDL and uric acid were found in intervention group at the end of the study. Catalase activity, LPO, and nitrites concentration in liver were significantly decreased, after the supplementation, together with elevated PON1 activity. Applied treatment significantly improved plasma lipid profile, liver FAs composition and parameters of oxidative stress in male Wistar rats.

Oxidized phospholipid-induced inflammation is mediated by Toll-like receptor 2

Oxidative tissue damage is a hallmark of many chronic inflammatory diseases. However, the precise mechanisms linking oxidative changes to inflammatory reactions remain unclear. Herein we show that Toll-like receptor 2 (TLR2) translates oxidative tissue damage into inflammatory responses by mediating the effects of oxidized phospholipids. Intraperitoneal injection of oxidized 1-palmitoyl-2-arachidonyl-sn-3-glycerophosphorylcholine (OxPAPC) resulted in upregulation of inflammatory genes in wild-type, but not in TLR2−/− mice. In vitro, OxPAPC induced TLR2 (but not TLR4)-dependent inflammatory gene expression and JNK and p38 signaling in macrophages. Induction of TLR2-dependent gene expression required reducible functional groups on sn-2 acyl chains of oxidized phospholipids, as well as serum cofactors. Finally, TLR2−/− mice were protected against carbon tetrachloride-induced oxidative tissue damage and inflammation, which was accompanied by accumulation of oxidized phospholipids in livers. Together, our findings demonstrate that TLR2 mediates cellular responses to oxidative tissue damage and they provide new insights into how oxidative stress is linked to acute and chronic inflammation.

Hepatic n-3 polyunsaturated fatty acid depletion promotes steatosis and insulin resistance in mice: genomic analysis of cellular targets.

Patients with non-alcoholic fatty liver disease are characterised by a decreased n-3/n-6 polyunsaturated fatty acid (PUFA) ratio in hepatic phospholipids. The metabolic consequences of n-3 PUFA depletion in the liver are poorly understood. We have reproduced a drastic drop in n-3 PUFA among hepatic phospholipids by feeding C57Bl/6J mice for 3 months with an n-3 PUFA depleted diet (DEF) versus a control diet (CT), which only differed in the PUFA content. DEF mice exhibited hepatic insulin resistance (assessed by euglycemic-hyperinsulinemic clamp) and steatosis that was associated with a decrease in fatty acid oxidation and occurred despite a higher capacity for triglyceride secretion. Microarray and qPCR analysis of the liver tissue revealed higher expression of all the enzymes involved in lipogenesis in DEF mice compared to CT mice, as well as increased expression and activation of sterol regulatory element binding protein-1c (SREBP-1c). Our data suggest that the activation of the liver X receptor pathway is involved in the overexpression of SREBP-1c, and this phenomenon cannot be attributed to insulin or to endoplasmic reticulum stress responses. In conclusion, n-3 PUFA depletion in liver phospholipids leads to activation of SREBP-1c and lipogenesis, which contributes to hepatic steatosis.

Effect of Synthetic Ligands of PPAR α, β/δ, γ, RAR, RXR and LXR on the Fatty Acid Composition of Phospholipids in Mice

Nuclear hormone receptors are transcription factors that can be activated by nutrition-derived ligands and alter the expression of various specific target genes. Stearoyl-Coenzyme A desaturase (SCD1) converts palmitic acid (16:0) to palmitoleic acid (16:1n-7) as well as stearic acid (18:0) to oleic acid (18:1n-9). At the same time, elongase 6 (ELOVL6) elongates 16:1n-7 and 18:1n-9 to vaccenic acid (18:1n-7) and eicosenoic acid (20:1n-9). We examined how synthetic selective ligands of nuclear hormone receptors alter the gene expression of hepatic enzymes in mice. In addition, we examined how the regulation of these two enzymes influences fatty acid composition of phospholipids in liver and plasma. Mice were gavaged daily for 1 week with synthetic ligands of peroxisome proliferator-activated receptor (PPAR) α, β/δ, γ, liver X receptor (LXR), retinoic acid receptor (RAR) and retinoid-X receptor (RXR) for 1 week. Phospholipids from liver and plasma were analysed using ESI-MS/MS and GC after saponification. Hepatic gene expression of SCD1 and ELOVL6 was measured using QRT-PCR. SCD1 and ELOVL6 expression increased after the gavage of LXR and RXR ligands. The analysis of fatty acid composition of total phospholipids in plasma and liver showed increased percentage contributions of the SCD1 and ELOVL6 products 18:1n-9, 18:1n-7 and 20:1n-9 after LXR and RXR ligand application. Analysis of total phospholipids from plasma and liver revealed a significant increase in monounsaturated fatty acids bound in phosphatidylcholine (PtdCho) and lysophosphatidylcholine (PtdEtn) after LXR and RXR ligand administration. Increased hepatic gene expression of SCD1 and ELOVL6 after gavage of selective RXR or LXR ligands to mice resulted in increased concentrations of their metabolic products in phospholipids of liver and plasma.

Up-regulated Desaturase and Elongase Gene Expression Promoted Accumulation of Polyunsaturated Fatty Acid (PUFA) but Not Long-Chain PUFA in Lates calcarifer, a Tropical Euryhaline Fish, Fed a Stearidonic Acid- and γ-Linoleic Acid-Enriched Diet

The limited activity of Δ6 fatty acid desaturase (FAD6) on α-linolenic (ALA, 18:3n-3) and linoleic (LA, 18:2n-6) acids in marine fish alters the long-chain (≥C(20)) polyunsaturated fatty acid (LC-PUFA) concentration in fish muscle and liver when vegetable oils replace fish oil (FO) in aquafeeds. Echium oil (EO), rich in stearidonic acid (SDA, 18:4n-3) and γ-linoleic acid (GLA, 18:3n-6), may enhance the biosynthesis of n-3 and n-6 LC-PUFA by bypassing the rate-limiting FAD6 step. Nutritional and environmental modulation of the mechanisms in LC-PUFA biosynthesis was examined in barramundi, Lates calcarifer , a tropical euryhaline fish. Juveniles were maintained in either freshwater or seawater and fed different dietary LC-PUFA precursors present in EO or rapeseed oil (RO) and compared with FO. After 8 weeks, growth of fish fed EO was slower compared to the FO and RO treatments. Irrespective of salinity, expression of the FAD6 and elongase was up-regulated in fish fed EO and RO diets, but did not lead to significant accumulation of LC-PUFA in the neutral lipid of fish tissues as occurred in the FO treatment. However, significant concentrations of eicosapentaenoic acid (EPA, 20:5n-3) and arachidonic acid (ARA, 20:4n-6), but not docosahexaenoic acid (DHA, 22:6n-3), appeared in liver and, to a lesser extent, in muscle of fish fed EO with marked increases in the phospholipid fraction. Fish in the EO treatment had higher EPA and ARA in their liver phospholipids than fish fed FO. Endogenous conversion of dietary precursors into neutral lipid LC-PUFA appears to be limited by factors other than the initial rate-limiting step. In contrast, phospholipid LC-PUFA had higher biosynthesis, or selective retention, in barramundi fed EO rather than RO.

Gene-activation mechanisms in the regression of atherosclerosis, elimination of diabetes type 2, and prevention of dementia.

Atherosclerotic vascular disease, diabetes mellitus (DM) and dementia are major global health problems. Both endogenous and exogenous factors activate genes functioning in biological processes. This review article focuses on gene-activation mechanisms that regress atherosclerosis, eliminate DM type 2 (DM2), and prevent cognitive decline and dementia. Gene-activating compounds upregulating functions of liver endoplasmic reticulum (ER) and affecting lipid and protein metabolism, increase ER size through membrane synthesis, and produce an antiatherogenic plasma lipoprotein profile. Numerous gene-activators regress atherosclerosis and reduce the occurrence of atherosclerotic disease. The gene-activators increase glucose disposal rate and insulin sensitivity and, by restoring normal glucose and insulin levels, remove metabolic syndrome and DM2. Patients with DM2 show an improvement of plasma lipoprotein profile and glucose tolerance together with increase in liver phospholipid (PL) and cytochrome (CYP) P450. The gene-activating compounds induce hepatic protein and PL synthesis, and upregulate enzymes including CYPs and glucokinase, nuclear receptors, apolipoproteins and ABC (ATP-binding cassette) transporters. They induce reparation of ER structures and eliminate consequences of ER stress. Healthy living habits activate mechanisms that maintain high levels of HDL and apolipoprotein AI, promote health, and prevent cognitive decline and dementia. Agonists of liver X receptor (LXR) reduce amyloid in brain plaques and improve cognitive performance in mouse models of Alzheimer`s disease. The gene activation increases the capacity to withstand cellular stress and to repair cellular damage and increases life span. Life free of major health problems and in good cognitive health promotes well-being and living a long and active life.

Influence of gender on DHA synthesis: the response of rat liver to low dietary α-linolenic acid evidences higher ω3 ∆4-desaturation index in females

The conversion rate of α-linolenic acid (ALA) into docosahexaenoic acid (DHA) is determined by dietary and non-dietary factors. Higher capacity of DHA synthesis has been evidenced in females, indicating that sex factors influence the conversion pathway. To evaluate the extent to which sexual dimorphism of DHA synthesis is subordinated to nutritional handling, we measured the ω3 ∆4-desaturation index in male and female rats receiving adequate or inadequate amounts of ALA. The ω3 ∆4-desaturation index was drawn from the DHA to docosapentaenoic acid (ω3DPA) ratio in liver phospholipids. Male and female rats born to ω3-deficient dams were fed a supplemented diet supplying low, inadequate, intermediate, or adequate ALA (5, 20, 100, or 300mg ALA/100g diet, respectively). Control rats from both gender received the adequate diet from fetal life. Compared with control, low ALA feeding induced the ω3 ∆4-desaturation index to increase by 38 and 70% in the phosphatidylethanolamine fraction of males and females, respectively, and by 67% in phosphatidylcholine in females only. Supplementations with increased doses of ALA progressively smoothed this gender effect. Moreover, the analysis of our data from a previous study shows that ovariectomy decreased, whereas estradiol treatment increased the ω3 index to values comparable with those of diet-matched males and intact females, respectively. Females are more prone than males to increase their index of ω3 ∆4-desaturation, especially in response to low supplies in ALA. Estradiol supports the ω3 index, suggesting that this hormone plays a role in the effect of gender on DHA synthesis.

Incorporation dynamics of dietary vegetable oil fatty acids into the triacylglycerols and phospholipids of tilapia (Oreochromis niloticus) tissues (fillet, liver, visceral fat and gonads)

Tilapia (Oreochromis niloticus) previously reared on a commercial feed were fed three experimental diets with added 60 g kg⁻¹ of soybean (SO), linseed (LO) or fish oils (FO), for 6 weeks. The final bodyweight (week 6) of fish was significantly lower when feeding the vegetable oils. At 0, 2, 4 and 6 weeks, fillet, liver, visceral fat, testis and ovary triacylglycerols (TAG) and phospholipids (PL) were analysed for their fatty acid (FA) composition. The simple FA dilution model has been successfully applied to describe the incorporation of numerous dietary FAs into both tissue TAGs and PLs. Fillet PL FAs reacted more sensitively on the FAs of the SO and LO diets, when compared to the TAGs. Alterations of the hepatic TAG and PL fractions were minor and less predictable. Testicular PLs have been found to preferentially accumulate n3 FAs, in particular docosahexaenoic acid (DHA) (C22:6 n3). In contrast, ovarian TAGs showed a predominant accretion of oleic acid by the FO diet. The increased dietary unsaturation index (SO, FO) was found to augment hepatic in vivo lipid peroxidation, as assessed by the tissue malondialdehyde concentrations.

Effects of lipid physicochemical characteristics on interrelations between lipid composition and the mouse liver index

Interrelations between the liver index (the relative mass) and various parameters of the liver lipid composition in 9 groups of intact female SHK mice sacrificed at different seasons and years group were studied depending on physicochemical characteristics of their lipids. There were revealed correlations between the liver index and the following parameters of the lipid composition: relative content of cardiolipin, lysoforms of the phospholipid/phosphatidylcholine ratio in liver phospholipids, and the [serine]/[phospholipids] molar ratio. The direction of these correlations has been established to depend on the lipid physicochemical characteristics. In all cases, there is observed a direct correlation if lipids have prooxidant properties and antiperoxide activity and an inverse correlation if lipids are characterized by antioxidant and antiperoxide activities.

The metabolic effects of di (2-ethyl hexyl) phthalate medium dose on lipid profiles in serum and liver tissue

Background: Di (2-ethyl hexyl) phthalate is the most widely used plasticizer in blood storage bag for transfusion. This substance can modify lipid metabolism. This study was aimed to elucidate the metabolic effects of di (2-ethyl hexyl) phthalate medium dose on lipid profiles in serum and liver tissue. Methods: Sprague Dawley rats were fed 1.0 % di (2-ethyl hexyl) phthalate diet (DEHP group, n=5) or a non-supplemented diet (control group, n=5) for 10 days. The rats were allowed to freely access each food. Serum lipid concentrations were measured using enzyme assay kits. Lipids of liver tissues were extracted and the lipid contents were determined. A peach of liver was prepared to determine the activities of malic enzyme and carnitine palmitoyl transferase-1 (CPT-1). Results: Serum lipid concentrations (mg/dL) of DEHP group decreased compared to control (P&lt;0.05). The serum triglyceride (TG) concentrations of control and DEHP groups were respectively (100.5±16.5) and (31.2±1.7); phospholipid (PL), (143.3±7.8) and (88.9±3.2); total cholesterol, (88.7±4.6) and (51.9±2.3). The liver TG content of control and DEHP group (mg/g liver) were respectively, (40.8±4.4) and (23.7±1.3); liver cholesterol were (3.36±0.29) and (2.33±0.23); and the liver PL were (36.5±1.0) and (41.7±0.6). Malic enzyme and CPT-1 activities (nmol/min/mg protein) of DEHP group increased compared to control (P&lt;0.05), in which their increases were approximately by 4.35- and 2.33-folds, respectively. Conclusion: The di (2-ethyl hexyl) phthalate medium dose attenuates lipids secretion from the liver cells into the bloodstream. The increase of liver PL level accompanied with the promotions of malic enzyme and the CPT-1 activities are the key factors of the dietary di (2-ethyl hexyl) phthalate effects in rats to attenuate the lipid secretions from the livers. (Med J Indones 2011; 20:20-6) Keywords: Di (2-ethyl hexyl) phthalate, hyperphospholipids, lipolysis, liver lipids, serum lipids

DDC-Induced Hepatic Protoporphyria and Changes in Serum and in Liver Lipids Content in Rat: Impact of Peripheral Benzodiazepine Receptor

ABSTRACTAdministration of DDC (3,5-diethoxycarbonil-1,4-dihydro-2,4,6-trimethylpyridine) (100 mg/kg, i.p.) to male rats produced significant increase in total porphyrins thus giving rise to the biochemical picture of porphyria(s). Porphyrins, accumulated in hepatic porphyria are putative endogenous ligands for peripheral benzodiazepine receptor. A role of peripheral benzodiazepine receptors in cholesterol transport and metabolism is suggested. Hepatic protoporphyria is associated with hepatomegaly, cholestasis and alterations in the microsomal cytochromes. We found that DDC administration in rat induced lipid disturbances and increased significantly total cholesterol in serum and in liver, as well as total phospholipids in liver. 27-Hydroxycholesterol content was significantly increased in serum and liver by DDC, while phenobarbital had no effect. We assume that the observed lipid disturbances are connected to the accumulation of porphyrins. These effects are probably modulated by porphyrin binding to peripheral benzodiazepine receptors.