linoleic-acid and Fatty-Liver

Triacylglycerol accumulation in the liver (fatty liver) caused by ethanol or carbon tetrachloride involves interactions with essential fatty acids and prostaglandins. The degree to which the fatty liver develops is dependent on total dietary fat intake. Both ethanol and carbon tetrachloride impair desaturation of linoleic acid and dihomo-gamma-linolenic acid and this appears to be relevant to the pathogenesis of fatty liver from two points of view. First, low arachidonic acid in liver phospholipids is associated with increased liver triacylglycerol content whether caused by ethanol, carbon tetrachloride, or essential fatty acid deficiency. Second, essential fatty acids including gamma-linolenic acid and arachidonic acid, as well as the prostaglandins, prevent ethanol- and carbon tetrachloride-induced fatty liver. Arachidonic acid and possibly the prostaglandins are therefore likely to be directly involved in lipoprotein and triacylglycerol secretion by the liver.

Topics: 8,11,14-Eicosatrienoic Acid; Animals; Arachidonic Acid; Arachidonic Acids; Carbon Tetrachloride; Cricetinae; Dietary Fats; Ethanol; Fatty Acids, Essential; Fatty Liver; Fatty Liver, Alcoholic; gamma-Linolenic Acid; Guinea Pigs; Humans; Linoleic Acid; Linoleic Acids; Linolenic Acids; Liver; Mice; Prostaglandins; Rats; Species Specificity; Triglycerides

Pentoxifylline (PTX) improved the histological features of nonalcoholic steatohepatitis (NASH) in a recent randomized placebo-controlled trial. However, the underlying mechanism responsible for the beneficial effects of PTX in NASH remains unidentified. A key role of lipid oxidation in the pathogenesis and progression of NASH has been established. PTX is known to decrease free-radical-mediated oxidative stress and inhibit lipid oxidation. The primary aim of this study was to evaluate the effects of PTX on levels of lipid oxidation products in patients with NASH. Levels of multiple structurally specific oxidized fatty acids including hydroxy-octadecadienoic acids (HODEs), oxo-octadecadienoic acids (oxoODEs), and hydroxy-eicosatetraenoic acids (HETEs) were quantified by mass spectrometry in plasma obtained at baseline and at study completion in patients who completed 1 year of therapy with PTX or placebo in a randomized controlled trial. Therapy with PTX resulted in significant decreases in 9-HODE and 13-oxoODE, oxidized lipid products of linoleic acid (LA) linked to histological severity in nonalcoholic fatty liver disease. Similarly, PTX therapy was associated with significant decreases in 8-HETE, 9-HETE, and 11-HETE compared to placebo. Statistically significant correlations were demonstrated between the decrease in HODEs and oxoODEs and improved histological scores of fibrosis and between the decrease in HETEs and improved lobular inflammation.. Therapy with PTX compared to placebo was associated with a significant reduction of oxidized fatty acids. This novel evidence supports that the beneficial effects of PTX in patients with NASH are likely partly mediated through decreasing lipid oxidation, largely free-radical-mediated lipid oxidation. Additionally, this is the first report on the link between decreased oxidized lipid products and improved histological disease in the setting of a therapeutic trial in NASH.

Topics: Adult; Biopsy, Needle; Blood Chemical Analysis; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Fatty Liver; Female; Follow-Up Studies; Humans; Immunohistochemistry; Insulin Resistance; Linoleic Acid; Lipid Metabolism; Lipid Peroxidation; Male; Middle Aged; Multivariate Analysis; Non-alcoholic Fatty Liver Disease; Patient Selection; Pentoxifylline; Prospective Studies; Reference Values; Severity of Illness Index; Statistics, Nonparametric; Treatment Outcome

To evaluate the effects of fatty acids on endoplasmic reticulum (ER) stress, oxidative stress, and lipid damage. We treated BRL3A rat liver cells with, linoleic (LA), linolenic, oleic (OA), palmitic (PA), palmitoleic (POA), or stearic (SA) acid for 12 hr. The characteristics of cell lipid deposition, oxidative stress indexes, ER stress markers, nuclear factor κB p65 (NF-κB p65), lipid synthesis and transport regulators, and cholesterol metabolism regulators were analyzed. Endoplasmic chaperones like glucose-regulated protein 78, CCAAT-enhancer-binding protein, NF-κB p65, hydrogen peroxide, and malonaldehyde in PA- and SA-treated cells were significantly higher than in other treated cells. Deposition of fatty acids especially LA and POA were significantly increased than in other treated cells. De novo lipogenesis regulators sterol regulatory element-binding protein 1c, fatty acid synthase, and acetyl-coenzyme A carboxylase 1 (ACC1) expression were significantly increased in all fatty acid stimulation groups, and PA- and SA-treated cells showed lower p-ACC1 expression and higher scd1 expression than other fatty acid groups. Very low-density lipoprotein synthesis and apolipoprotein B100 expression in free fatty acids treated cells were significantly lower than control. PA, SA, OA, and POA had shown significantly increased cholesterol synthesis than other treated cells. PA and SA showed the lower synthesis of cytochrome P7A1 and total bile acids than other fatty acids treated cells. Excess of saturated fatty acids led to severe ER and oxidative stress. Excess unsaturated fatty acids led to increased lipid deposition in cultured hepatocytes. A balanced fatty acid intake is needed to maintain lipid homeostasis.

Topics: Acetyl-CoA Carboxylase; alpha-Linolenic Acid; Animals; Cells, Cultured; Endoplasmic Reticulum Stress; Fatty Acid Synthases; Fatty Acids; Fatty Liver; Hepatocytes; Humans; Linoleic Acid; Lipid Metabolism; Lipids; Lipogenesis; Lipoproteins, VLDL; Liver; Oleic Acid; Oxidative Stress; Palmitic Acid; Rats; Stearic Acids

Retinol-binding protein 4 (RBP4) serves as a transporter for all- trans-retinol (1) in the blood, and it has been proposed to act as an adipokine. Elevated plasma levels of the protein have been linked to diabetes, obesity, cardiovascular diseases, and nonalcoholic fatty liver disease (NAFLD). Recently, adipocyte-specific overexpression of RBP4 was reported to cause hepatic steatosis in mice. We previously identified an orally bioavailable RBP4 antagonist that significantly lowered RBP4 serum levels in Abca4

Topics: Animals; Chemistry Techniques, Synthetic; Disease Models, Animal; Drug Design; Fatty Liver; Male; Mice; Piperidines; Rats; Retinol-Binding Proteins, Plasma; Tissue Distribution

The goose liver is an ideal model for deciphering lipogenesis molecular mechanisms. This study was designed to investigate the effect of different lipid sources on hepatic lipogenesis in overfed geese. Sixty Landes geese were fed ad libitum with no fat (control) or overfed diets containing 2% goose fat (GF) or rapeseed oil (RO) for 20 days. We measured fatty acid composition of the liver at day 20 of overfeeding. We performed a transcriptomic comparison of fatty liver between GF and RO-fed geese to gain insights into the molecular and cellular events mediating lipogenesis activity. The results showed that there was no substantial effect on fatty liver performance between GF- and RO-fed geese. Significant differences in fatty acid composition were detected between GF- and RO-fed geese. Total ω-6 PUFAs increased and saturated fatty acid decreased (P < 0.05) with RO supplementation when compared with GF, but ω-3 PUFAs did not differ between the two diets. Concentrations of C16:1, C18:1, C18:2, C20:2, and C22:1 were higher (P < 0.05) in the fatty liver of RO-fed geese compared to those in the GF group. Analysis of transcriptome sequencing showed that there were 124 up-regulated and 129 down-regulated differentially expressed genes in the fatty liver of RO and GF-fed geese. Many of these genes code for proteins involved in the lipid metabolic process, including bile secretion, adipocytokine signalling pathway, biosynthesis of unsaturated fatty acids, linoleic acid metabolism, fatty acid elongation and fatty acid biosynthesis, and fat digestion and absorption. Moreover, genes involved in lipid-related pathways such as peroxisome, steroid biosynthesis, steroid hormone biosynthesis, retinol metabolism, and apoptosis were altered, suggesting that the fatty liver of goose fed different oils undertakes both an oxidation function and hormone-related metabolic function. In conclusions, these data suggest that RO supplementation reduces liver lipid oxidation and improves lipogenesis. These findings provide new insights into the molecular mechanisms involved in fatty liver formation and provide valuable resources for analysing mechanisms underlying the effects of oils from different sources on the goose fatty liver.

Topics: Animals; Apoptosis; Brassica rapa; Fatty Acids, Unsaturated; Fatty Liver; Geese; Gene Expression Profiling; Gene Expression Regulation; Hormones; Inflammation; Linoleic Acid; Lipids; Organ Size; Oxygen; Peroxisomes; Plant Oils; Polymerase Chain Reaction; Protein Interaction Mapping; Transcriptome; Vitamin A

Nonalcoholic fatty liver is characterized by the abnormal accumulation of triglycerides within hepatocytes, resulting in a steatotic liver. Glucagon-like peptide 1 and its analog exendin-4 can ameliorate certain aspects of this syndrome by inducing weight loss and reducing hepatic triglyceride accumulation, but it is unclear whether these effects result from the effects of glucagon-like peptide 1 on the pancreas, or from direct action on the liver. This study investigated the direct action and putative cellular mechanism of exendin-4 on steatotic hepatocytes in culture. Steatosis was induced in cultured HepG2 human hepatoma cells by incubation in media supplemented with 2 mM each of linoleic acid and oleic acid. Steatotic hepatocytes were then pre-incubated in the protein kinase A inhibitor H89 for 30 min, then treated with exendin-4 over a period of 24 h. Cell viability and triglyceride content were characterized by a TUNEL assay and AdipoRed staining, respectively. Our results showed that steatotic cells maintained high levels of intracellular triglycerides (80%) compared to lean controls (25%). Exendin-4 treatment caused a significant reduction in intracellular triglyceride content after 12 h that persisted through 24 h, while protein kinase A inhibitors abolished the effects of exendin-4. The results demonstrate the exendin-4 induces a partial reduction in triglycerides in steatotic hepatocytes within 12 h via the GLP-1 receptor-mediated activation of protein kinase A. Thus, the reduction in hepatocyte triglyceride accumulation is likely driven primarily by downregulation of lipogenesis and upregulation of β-oxidation of free fatty acids.

Topics: Carcinoma, Hepatocellular; Cell Survival; Cyclic AMP-Dependent Protein Kinases; Exenatide; Fatty Liver; Glucagon-Like Peptide 1; Hep G2 Cells; Hepatocytes; Humans; Isoquinolines; Linoleic Acid; Lipogenesis; Liver Neoplasms; Oleic Acid; Pancreas; Peptides; Sulfonamides; Triglycerides; Venoms

The immune system acts on different metabolic tissues that are implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Leptin and linoleic acid have the ability to potentially affect immune cells, whereas curcumin is a known natural polyphenol with antioxidant and anti-inflammatory properties.. This study was designed to evaluate the pro-inflammatory and pro-oxidant effects of leptin and linoleic acid on immune cells from patients with NAFLD and to corroborate the modulatory effects of curcumin and its preventive properties against the progression of NAFLD using a high-fat diet (HFD)-induced NAFLD/nonalcoholic steatohepatitis mouse model.. The ex vivo experiments showed that linoleic acid increased the production of reactive oxygen species in monocytes and liver macrophages, whereas leptin enhanced tumor necrosis factor-α (TNF-α) production in monocytes and interferon-γ production in circulating CD4+ cells. Conversely, oral administration of curcumin prevented HFD-induced liver injury, metabolic alterations, intrahepatic CD4+ cell accumulation and the linoleic acid- and leptin- induced pro-inflammatory and pro-oxidant effects on mouse liver macrophages.. Our findings provide new evidence for the therapeutic potential of curcumin to treat human NAFLD. However, the development of a preventive treatment targeting human circulating monocytes and liver macrophages as well as peripheral and hepatic CD4+ cells requires additional research.

Topics: Animals; Antioxidants; CD4-Positive T-Lymphocytes; Curcumin; Diet, High-Fat; Disease Models, Animal; Fatty Liver; Hepatocytes; Humans; Leptin; Linoleic Acid; Liver; Mice; Non-alcoholic Fatty Liver Disease; Reactive Oxygen Species

Δ-6-fatty acid desaturase (FADS2) is the key enzyme in the biosynthesis of polyunsaturated fatty acids (PUFAs), the essential structural determinants of mammalian membrane lipid-bilayers. We developed the auxotrophic fads2(-/-) mouse mutant to assess the enigmatic role of ω3- and ω6-PUFAs in lipid homeostasis, membrane structure and function. Obesity resistance is another major phenotype of the fads2(-/-) mutant, the molecular basis of which is unknown. Phospholipidomic profiling of membrane systems of fads2(-/-)mice revealed diacylglycerol-structures, deprived of PUFAs but substituted with surrogate eicosa-5,11,14-trienoic acid. ω6-Arachidonic (AA) and ω3-docosahexaenoic acid (DHA) supplemented diets transformed fads2(-/-) into AA-fads2(-/-) and DHA-fads2(-/-) mutants. Severely altered phospholipid-bilayer structures of subcellular membranes of fads2(-/-) liver specifically interfered with maturation of transcription factor sterol-regulatory-element-binding protein, the key regulator of lipogenesis and lipid homeostasis. This study strengthens the concept that specific PUFA-substituted membrane phospholipid species are critical constituents of the structural platform operative in lipid homeostasis in normal and disease conditions.

Topics: Adipocytes, White; Adipose Tissue, White; Animals; Arachidonic Acid; Cell Size; Disease Resistance; Docosahexaenoic Acids; Fatty Liver; Female; Linoleic Acid; Linoleoyl-CoA Desaturase; Lipogenesis; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Phospholipids; Transcriptome; Weight Gain

Our aim was to investigate the effects of trans-fatty acids (TFA) on liver lipid metabolism in mice fed on experimental diets rich in either oleic or linoleic acid.. Twenty-two male CF1 mice (22.0 ± 0.1 g) were fed with diets rich in corn oil or olive oil, supplemented or not with TFA (0.75 g TFA/100 g diet), for 4 weeks. Changes in triacylglycerol content, the activity and expression of enzymes involved in lipogenesis and fatty acid oxidation were measured.. Supplementation of an olive oil-rich diet with TFA increased liver triacylglycerols, the activity and expression of lipogenic enzymes and sterol regulatory element-binding protein SREBP-1a expression. By contrast, when TFA were added to a corn oil-rich diet, they did not modify these parameters. No significant differences were observed among the experimental groups in the activity and expression of carnitine palmitoyltransferase-Ia, body and liver weights or serum triacylglycerol concentrations.. The effect of TFA on liver fat accumulation depends on the dietary fatty acid composition. Steatosis induced by TFA when included in an olive oil diet (but not in a corn oil diet) was associated with an increased lipogenesis but not with a decreased fatty acid oxidation in animals fed on the olive oil diet. This metabolic change is mediated by SREBP-1a but not by SREBP-1c, and seems to be independent of insulin.

Topics: Animals; Corn Oil; Dietary Fats; Fatty Liver; Gene Expression Regulation; Hydrogenation; Linoleic Acid; Lipid Metabolism; Lipogenesis; Liver; Male; Mice; Mice, Inbred Strains; Oleic Acid; Olive Oil; Oxidation-Reduction; Plant Oils; Random Allocation; Sterol Regulatory Element Binding Protein 1; Trans Fatty Acids; Triglycerides

Oxidative stress is a core abnormality responsible for disease progression in nonalcoholic fatty liver disease (NAFLD). However, the pathways that contribute to oxidative damage in vivo are poorly understood. Our aims were to define the circulating profile of lipid oxidation products in NAFLD patients, the source of these products, and assess whether their circulating levels reflect histological changes in the liver. The levels of multiple structurally specific oxidized fatty acids, including individual hydroxy-eicosatetraenoic acids (HETE), hydroxy-octadecadenoic acids (HODE), and oxo-octadecadenoic acids (oxoODE), were measured by mass spectrometry in plasma at time of liver biopsy in an initial cohort of 73 and a validation cohort of 49 consecutive patients. Of the markers monitored, 9- and 13-HODEs and 9- and 13-oxoODEs, products of free radical-mediated oxidation of linoleic acid (LA), were significantly elevated in patients with nonalcoholic steatohepatitis (NASH), compared with patients with steatosis. A strong correlation was revealed between these oxidation products and liver histopathology (inflammation, fibrosis, and steatosis). Further analyses of HODEs showed equivalent R and S chiral distribution. A risk score for NASH (oxNASH) was developed in the initial clinical cohort and shown to have high diagnostic accuracy for NASH versus steatosis in the independent validation cohort. Subjects with elevated oxNASH levels (top tertile) were 9.7-fold (P < 0.0001) more likely to have NASH than those with low levels (bottom tertile). Collectively, these findings support a key role for free radical-mediated linoleic acid oxidation in human NASH and define a risk score, oxNASH, for noninvasive detection of the presence of NASH.

Topics: Cohort Studies; Fatty Acids, Unsaturated; Fatty Liver; Humans; Hydroxyeicosatetraenoic Acids; Linoleic Acid; Lipid Metabolism; Lipids; Non-alcoholic Fatty Liver Disease; Spectrometry, Mass, Electrospray Ionization

The susceptibility to develop hepatic steatosis is known to differ between duck species, especially between Muscovy and Pekin ducks. This difference could be explained by either differential responses of species to overfeeding or genetic differences in hepatic lipid metabolism. The aim of the present study was to compare the intensities of the different hepatic pathways (oxidation, lipogenesis, esterification, secretion, etc.) of the two main nutrients (glucose and linoleic acid (LA)) reaching the liver of ad libitum-fed Muscovy (n 6) and Pekin (n 6) ducks using the ex vivo method of liver slices incubated for 16 h with [U-14C]glucose, [1-14C]LA and [35S]methionine added to the survival medium. In such experimental conditions, the lipogenesis pathway from glucose was 2-fold higher (P<0.05) in the liver of the Muscovy duck than in that of the Pekin duck. Furthermore, the hepatic uptake of LA was 2-fold higher (P<0.05) in the Muscovy duck than in the Pekin duck leading to a 2-fold higher (P<0.05) esterification of this fatty acid in the liver of the Muscovy duck. The hepatic secretion of VLDL was higher (P<0.01) in the Muscovy duck than in the Pekin duck but insufficient to prevent lipid accumulation in the liver of the Muscovy duck. In conclusion, these results show the influence of the species on the hepatic metabolism of ducks in relation to their susceptibility to develop fatty liver. These results should shed light on the metabolic regulations that might underlie susceptibility to hepatic steatosis in the the human liver.

Topics: Animal Feed; Animals; Disease Susceptibility; Ducks; Fatty Liver; Genotype; Glucose; Linoleic Acid; Lipoproteins, VLDL; Liver; Methionine; Models, Animal; Poultry Diseases; Species Specificity; Tissue Culture Techniques

Trans-10, cis-12-conjugated linoleic acid (CLA)-enriched diets promote fatty liver in mice, while cis-9, trans-11-CLA ameliorates this effect, suggesting regulation of multiple genes. To test this hypothesis, apoE-deficient mice were fed a Western-type diet enriched with linoleic acid isomers, and their hepatic gene expression was analyzed with DNA microarrays. To provide an initial screening of candidate genes, only 12 with remarkably modified expression between both CLA isomers were considered and confirmed by quantitative RT-PCR. Additionally mRNA expression of 15 genes involved in lipid metabolism was also studied. Ten genes (Fsp27, Aqp4, Cd36, Ly6d, Scd1, Hsd3b5, Syt1, Cyp7b1, and Tff3) showed significant associations among their expressions and the degree of hepatic steatosis. Their involvement was also analyzed in other models of steatosis. In hyperhomocysteinemic mice lacking Cbs gene, only Fsp27, Cd36, Scd1, Syt1, and Hsd3b5 hepatic expressions were associated with steatosis. In apoE-deficient mice consuming olive-enriched diet displaying reduction of the fatty liver, only Fsp27 and Syt1 expressions were found associated. Using this strategy, we have shown that expression of these genes is highly associated with hepatic steatosis in a genetic disease such as Cbs deficiency and in two common situations such as Western diets containing CLA isomers or a Mediterranean-type diet.. The results highlight new processes involved in lipid handling in liver and will help to understand the complex human pathology providing new proteins and new strategies to cope with hepatic steatosis.

Topics: Animals; Apolipoproteins E; Aquaporin 4; Blotting, Western; CD36 Antigens; Cystathionine beta-Synthase; Cytochrome P450 Family 7; Fatty Liver; Female; Gene Expression Profiling; Gene Expression Regulation; Genetic Predisposition to Disease; GTPase-Activating Proteins; Isomerism; Linoleic Acid; Liver; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Oligonucleotide Array Sequence Analysis; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Stearoyl-CoA Desaturase; Steroid Hydroxylases

Topics: Adiposity; Animals; Dietary Fats; Dietary Sucrose; Disease Models, Animal; Fatty Liver; Linoleic Acid; Physical Conditioning, Animal; Rats

To study the effects of trans-10,cis-12 conjugated linoleic acid (CLA) on liver size and composition, as well as on hepatic lipogenesis and fatty acid oxidation, in adult hamsters.. Sixteen male Syrian Golden hamsters (8-month-old; initial body weight 167 +/- 5 g) were divided into two groups and fed on atherogenic diets supplemented either with 0.5% linoleic acid or trans-10,cis-12 CLA, for 6 weeks. Liver lipids, fatty acid profile, protein, water and DNA contents were analysed. The activity and expression of several enzymes involved in liver fatty oxidation and lipogenesis were assessed, as was the expression of transcriptional factors controlling these enzymes.. The addition of CLA to the diet led to significantly greater liver weight due to hyperplasia. No changes were observed in liver composition. CLA did not modify the expression or the activity of analysed oxidative enzymes. With regard to lipogenic enzymes, an increase in the expression and the activity of acetyl-CoA carboxylase was found.. These results show that the expected body fat-lowering effect of trans-10,cis-12 CLA, observed in young rodents, is not found in adult hamsters. The lack of increase in liver fatty acid oxidation, help to explain why that effect was not found in these animals. Further, the CLA treatment-induced hepatomegaly is a consequence of hyperplasia.

Topics: Acetyl-CoA Carboxylase; Age Factors; Animals; Cricetinae; Diet, Atherogenic; Dietary Fats; Fatty Liver; Hepatomegaly; Hyperplasia; Linoleic Acid; Linoleic Acids, Conjugated; Lipid Metabolism; Liver; Male; Mesocricetus; Organ Size; Oxidoreductases

Hyperlipidemia is the major risk factors of heart disease such as atherosclerosis, stroke, and death. In the present study, we studied the effect of gallic acid (GA), linoleic acid (LA), mixture of GA and LA (MGL), and chemically synthesized gallic acid-linoleic acid ester (octadeca-9,12-dienyl-3,4,5-trihydroxybenzoate, GLE) on the ability to ameliorate hyperlipidemia in C57BL/6 mice fed a high-fat diet (HFD). GLE, GA, LA, and MGL were mixed with HFD and the composition of the test compounds were 1% of the diet for 7 weeks. After 7 weeks, the average body weight of ND and GLE groups was lower than that of HFD group (P<0.05). The liver weight of mice decreased (P<0.05) in all treatment groups relative to HFD fed group. The plasma lipids such as triglyceride and LDL-cholesterol were found to be decreased (P<0.05) in GLE, GA, LA, and MGL fed mice when compared to that of HFD fed mice. But high-density lipoprotein (HDL) cholesterol increased (P<0.05) in HFD and GLE fed mice when compared to that of ND fed mice. The hepatic accumulation of fat droplets of GA, LA, GLE, and MGL group showed considerably lower than that of HFD group. Adipose histology showed that GLE supplementation was found to be more effective in decreasing the size of adipocyte relative to those of other treatment groups. In conclusion, the supplementation of synthetic GLE from gallic acid and linoleic acid ester may have a potential hypolipidemic effect on mice fed high-fat diet. Further studies are required to prove GLE as a hypolipidemic agent.

Topics: Adipocytes; Adipose Tissue; Animals; Body Weight; Cell Nucleus; Cholesterol, HDL; Cholesterol, LDL; Dietary Fats; Disease Models, Animal; Fatty Liver; Female; Gallic Acid; Hyperlipidemias; Hypolipidemic Agents; Linoleic Acid; Lipids; Liver; Mice; Mice, Inbred C57BL; Obesity; Triglycerides

There are genetic differences in the hepatic glucose and linoleic acid metabolisms between Muscovy and Pekin ducks ad libitum-fed. To understand the effect of overfeeding on the hepatic metabolisms in these two species of ducks, we compared the different pathways of glucose and linoleic acid reaching the liver of Muscovy (Cairina moschata) (n=6) and Pekin (Anas platyrhynchos) (n=6) ducks overfed for 1 week and sacrificed 2-4 h after their last meal by using the ex vivo method of liver slices incubated for 16 h with [U-(14)C]-glucose, [1-(14)C]-linoleic acid and [(35)S]-methionine added to the survival medium. The glucose was the main precursor of triacylglycerol synthesis in the liver of these two species and its hepatic metabolism was similar between species. The hepatic uptake of linoleic acid was 1.7-fold higher (P=0.020) in the Muscovy duck than in the Pekin duck leading to a 1.9-fold higher (P=0.017) esterification of this fatty acid in the liver of the Muscovy duck than in that of the Pekin duck. Finally, both species after 1 week of overfeeding exhibited the same capacity to secrete VLDL remaining insufficient to avoid hepatic steatosis.

Topics: Animals; Ducks; Eating; Fatty Liver; Glucose; In Vitro Techniques; Linoleic Acid; Lipoproteins, VLDL; Liver; Male; Methionine; Species Specificity

Nonalcoholic fatty liver disease (NAFLD) is the preferred term to describe the spectrum of liver damage ranging from hepatic steatosis to steatohepatitis, liver fibrosis, and cirrhosis, and it is emerging as the most common liver disease in industrialized countries. Thus, the discovery of food components that would ameliorate NAFLD is of interest. Conjugated linoleic acid (CLA), a mixture of positional and geometric isomers of linoleic acid, has attracted considerable attention because of its potentially beneficial biological effects both in vitro and in vivo. We tested whether dietary CLA protects Zucker (fa/fa) rats from hepatic injury. After 8 wk of feeding, hepatomegaly, hepatic triglyceride (TG) accumulation, and elevated hepatic injury markers in plasma were markedly alleviated in CLA-fed Zucker rats compared with linoleic acid-fed (control) rats. These effects were attributed in part to the enhanced hepatic activities of carnitine palmitoyltransferase, a key enzyme of fatty acid beta-oxidation, and microsomal TG transfer protein, an important factor for lipoprotein secretion due to the CLA diet. We previously reported that the severe hyperinsulinemia in control Zucker rats was attenuated in CLA-fed rats due to an enhanced level of plasma adiponectin, which improves insulin sensitivity. In the present study, the adiponectin concentration was increased and the mRNA expression of tumor necrosis factor-alpha, an inflammatory cytokine, was markedly suppressed in the liver of CLA-fed Zucker rats. We speculate that the enhanced level of liver adiponectin may prevent the development and progression of NAFLD in CLA-fed Zucker rats.

Topics: Adiponectin; Animal Feed; Animals; Diet; Fatty Liver; Intercellular Signaling Peptides and Proteins; Linoleic Acid; Rats; Rats, Zucker; RNA, Messenger

We compared the efficacy of alpha-linolenic acid (alpha-LNA, n-3) and linoleic acid (LA, n-6) on orotic acid (OA)-induced fatty liver in Sprague-Dawley rats. Rats were fed semi-synthetic diets containing either LA or alpha-LNA with or without 1% OA for 2 wk. OA supplementation lowered serum lipids in LA+OA groups. In addition to the decline of serum lipids in alpha-LNA groups compared to LA groups, a further decrease was found in alpha-LNA+OA groups compared to LA+OA groups. OA-containing diets significantly increased the liver weights and triacylglycerol (TG) accumulations compared with the OA-free diets. These results were attributed to the significant increases in the activities of phosphatidate phosphohydrolase (PAP), a rate-limiting enzyme of TG synthesis, and glucose-6-phosphate dehydrogenase, a fatty acid synthesis-related enzyme. However, the increase of PAP activity was significantly less in the alpha-LNA+OA group as compared with the LA+OA group. These results suggest that dietary alpha-LNA alleviates OA-induced hepatic TG accumulation through the attenuation of hepatic TG synthesis in rats.

Topics: alpha-Linolenic Acid; Animals; Fatty Liver; Linoleic Acid; Male; Organ Size; Orotic Acid; Phosphatidate Phosphatase; Random Allocation; Rats; Rats, Sprague-Dawley; Triglycerides

Conjugated 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-C(18:2) (CLA2) and not cis-9,trans-11-C(18:2) (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 triglyceridaemia only.

Topics: Animals; Base Sequence; Body Weight; DNA Primers; Esterification; Fatty Acids; Fatty Liver; Linoleic Acid; Lipoproteins, VLDL; Liver; Mice; Mice, Inbred C57BL; Myocardium; RNA, Messenger; Triglycerides

To develop a method to preserve lipids in formalin-fixed tissues for staining in paraffin sections, and to illustrate its use in lung and brain of a fat embolism case, and in examples of fatty liver and atheroma.. A saturated solution of linoleic acid in 70% ethylene glycol was prepared and tissues were exposed to this for 3 days at 56 degrees C. These tissues were treated with 2% chromic acid at 4 degrees C for 24 h followed by 24 h in 5% sodium bicarbonate, with appropriate rinsing between solutions. Paraffin sections of these tissues were stained with a lipid-soluble dye such as Oil Red O. Examples of fat embolism, fatty liver, and atheroma were shown photographically as illustrations of expected results.. The demonstration of fat embolism with good quality tissue detail is made practical by the method, which is convenient and inexpensive. The method appears to be generally applicable to tissue lipids of various sorts, as exemplified by adipose tissue, fatty liver, and atheroma.

Topics: Adipocytes; Arteriosclerosis; Azo Compounds; Brain; Chromates; Embolism, Fat; Ethylene Glycol; Fatty Liver; Humans; Linoleic Acid; Lipids; Lung; Microscopy, Electron; Myocytes, Smooth Muscle; Paraffin Embedding; Sodium Bicarbonate; Tissue Fixation

Conjugated linoleic acids (CLA) are a class of positional, geometric, conjugated dienoic isomers of linoleic acid (LA). Dietary CLA supplementation results in a dramatic decrease in body fat mass in mice, but also causes considerable liver steatosis. However, little is known of the molecular mechanisms leading to hepatomegaly. Although c9,t11- and t10,c12-CLA isomers are found in similar proportions in commercial preparations, the respective roles of these two molecules in liver enlargement has not been studied. We show here that mice fed a diet enriched in t10,c12-CLA (0.4% w/w) for 4 weeks developed lipoatrophy, hyperinsulinemia, and fatty liver, whereas diets enriched in c9,t11-CLA and LA had no significant effect. In the liver, dietary t10,c12-CLA triggered the ectopic production of peroxisome proliferator-activated receptor gamma (PPARgamma), adipocyte lipid-binding protein and fatty acid transporter mRNAs and induced expression of the sterol responsive element-binding protein-1a and fatty acid synthase genes. In vitro transactivation assays demonstrated that t10,c12- and c9,t11-CLA were equally efficient at activating PPARalpha, beta/delta, and gamma and inhibiting liver-X-receptor. Thus, the specific effect of t10,c12-CLA is unlikely to result from direct interaction with these nuclear receptors. Instead, t10,c12-CLA-induced hyperinsulinemia may trigger liver steatosis, by inducing both fatty acid uptake and lipogenesis.

Topics: Adipose Tissue; Animals; Body Composition; Body Weight; Dietary Fats; DNA-Binding Proteins; Energy Metabolism; Fatty Liver; Female; Gene Expression Regulation; Hyperinsulinism; Insulin; Isomerism; Linoleic Acid; Liver; Liver X Receptors; Mice; Orphan Nuclear Receptors; Receptors, Cytoplasmic and Nuclear; RNA, Messenger; Transcription Factors

We investigated the composition of fatty acids in adipose tissue, serum, and liver of cows that were fed at restricted energy intake or were overfed during the dry period. Overfed cows had higher concentrations of serum nonesterified fatty acids and consequently accumulated greater amounts of triacylglycerols in the liver than did cows that were fed at restricted energy intake. The percentages of the different fatty acids present in adipose tissue were similar for both groups and did not change during sampling intervals. Before parturition, concentrations of the individual fatty acids present in serum were similar between groups. After parturition, concentrations of major fatty acids in serum, including palmitic, stearic, oleic, and linoleic acids significantly increased in both groups and were higher in overfed cows than in cows that were fed at restricted energy intake. The shift of concentrations of the different fatty acids present in the liver--as a result of increased lipolysis-was observed in palmitic, oleic, and linoleic acids but not stearic acid, suggesting that stearic acid is used by the liver (i.e., oxidation) or is considerably secreted through the milk, thereby not increasing in accumulation in the liver. In conclusion, different feeding regimens during the dry period do not influence the composition of fatty acids in adipose tissue. More intensive lipolysis results in increased concentrations of palmitic, stearic, oleic, and linoleic acids in the blood; subsequently, these fatty acids, excluding stearic acid, greatly accumulated in the liver.

Topics: Adipose Tissue; Animals; Cattle; Cattle Diseases; Diet; Energy Intake; Fatty Acids; Fatty Acids, Nonesterified; Fatty Liver; Female; Linoleic Acid; Lipolysis; Liver; Oleic Acid; Palmitic Acid; Puerperal Disorders; Stearic Acids; Triglycerides; Weight Gain

The present study compared the hepatic fatty acid composition of cows that were fed a high energy diet during the dry period to induce fatty liver after parturition with that of control cows. Treated cows had higher concentrations of plasma nonesterified fatty acids as a result of greater lipolysis after parturition than did control cows; consequently, the treated cows accumulated greater amounts of triacylglycerols in the liver. Before parturition, treated cows had lower percentages of oleic acid and higher percentages of linoleic acid than did control cows, but percentages of other fatty acids were similar for both groups. After parturition, percentages of each fatty acid were changed substantially, particularly the four major fatty acids (palmitic, stearic, oleic, and linoleic acids). For treated cows, the percentages of palmitic and oleic acids were higher at 0.5 wk after parturition than at 1 wk before parturition; percentages of stearic and linoleic acids decreased. Unlike treated cows, the percentages of both oleic and linoleic acids in the control cows did not change during that time. Moreover, we found that when lipolysis decreased, as indicated by lower plasma nonesterified fatty acid concentrations, the percentages of each fatty acid gradually rebounded toward the concentrations measured before parturition; this observation indicates that the shift in hepatic fatty acid composition is influenced by lipolysis. The increased lipolysis after parturition led to a vast increase in the hepatic triacyglycerol concentration and to a shift in hepatic fatty acid composition.

Topics: 3-Hydroxybutyric Acid; Animals; Cattle; Cattle Diseases; Energy Intake; Fatty Acids; Fatty Acids, Nonesterified; Fatty Liver; Female; Glycogen; Linoleic Acid; Lipolysis; Liver; Oleic Acid; Palmitic Acid; Pregnancy; Stearic Acids; Triglycerides

Topics: Acetates; Carbon Isotopes; Fatty Acids; Fatty Liver; Glucosephosphate Dehydrogenase; Glycerides; Ligases; Linoleic Acid; Lipid Metabolism; Liver; Palmitic Acid; Phospholipids; Radiometry; Rats; Research; Starvation

Topics: Chemical and Drug Induced Liver Injury; Cholesterol; Chromatography; Fatty Acids; Fatty Acids, Essential; Fatty Liver; Geriatrics; Hepatitis; Hypervitaminosis A; Linoleic Acid; Lipid Metabolism; Lipids; Liver; Oleic Acid; Palmitic Acid; Phospholipids; Toxicology; Vitamin K

Topics: Choline; Choline Deficiency; Dietary Fats; Dietary Proteins; Fatty Acids; Fatty Acids, Essential; Fatty Liver; Fish Oils; Histocytochemistry; Linoleic Acid; Lipid Metabolism; Lipids; Oleic Acid; Palmitic Acid; Proteins; Rats; Research; Stearic Acids

Topics: Acetates; Blood Chemical Analysis; Carbon Isotopes; Cholesterol; Electrophoresis; Fatty Acids; Fatty Acids, Essential; Fatty Liver; Histocytochemistry; Isoleucine; Linoleic Acid; Lipid Metabolism; Lipoproteins; Liver; Liver Glycogen; Nitrogen; Oleic Acid; Palmitic Acid; Phospholipids; Protein Deficiency; Proteins; Rats; Research; Stearic Acids

Topics: Dietary Fats; Fatty Acids; Fatty Acids, Essential; Fatty Liver; Linoleic Acid; Lipids; Lysine; Metabolism; Oleic Acid; Palmitic Acid; Phospholipids; Protein Deficiency; Rats; Research; Stearic Acids; Threonine

Topics: Cholesterol; Chromatography; Cocos; Cottonseed Oil; Dietary Fats; Fatty Acids; Fatty Liver; Glycerides; Linoleic Acid; Linoleic Acids; Lipids; Oils; Oleic Acid; Oleic Acids; Palmitic Acid; Pathology; Phospholipids; Rats; Research; Toxicology