Consumption of mate tea (Ilex paraguariensis) decreases the oxidation of unsaturated fatty acids in mouse liver

Mate (Ilex paraguariensis) is rich in polyphenolic compounds, which are thought to contribute to the health benefits of tea. Mate tea was administered orally to mice at a dose of 0.5, 1.0 or 2.0 g/kg for 60 d, and changes both in serum lipid concentration and fatty acid composition of liver and kidney were examined. The effects of mate tea on serum and tissue lipid peroxidation were assessed by the evaluation of thiobarbituric acid-reactive substances (TBARS). In tea-consuming mice, both MUFA (18: 1n-9) and PUFA (18: 2n-6 and 20: 4n-6) were increased (P<0.05) in the liver lipid (approximately 90 and 60%, respectively), whereas only MUFA (approximately 20%) were increased in the kidney lipid. The most altered PUFA class was n-6 PUFA, which increased by approximately 60-75 % (P<0.05). This difference in the fatty acid profile in the liver is reflected in the increased PUFA:SFA ratio. Consistent with these results, mice fed with mate tea had much lower TBARS in the liver. No differences (P>0.05) were found in the levels of serum cholesterol, HDL-cholesterol and TAG under the conditions of the present study. These results suggest that treatment with mate tea was able to protect unsaturated fatty acids from oxidation and may have selective protective effects within the body, especially on the liver.

Soluble CD163 is not increased in visceral fat and steatotic liver and is even suppressed by free fatty acids in vitro

Visceral fat differs from subcutaneous fat by higher local inflammation and increased release of IL-6 and free fatty acids (FFA) which contribute to hepatic steatosis. IL-6 has been shown to upregulate the monocyte/macrophage specific receptor CD163 whose soluble form, sCD163, is increased in inflammatory diseases. Here, it was analyzed whether CD163 and sCD163 are differentially expressed in the human fat depots and fatty liver. CD163 mRNA and protein were similarly expressed in paired samples of human visceral and subcutaneous fat, and comparable levels in portal venous and systemic venous blood of liver-healthy controls indicate that release of sCD163 from visceral adipose tissue was not increased. CD163 was also similarly expressed in steatotic liver when compared to non-steatotic tissues and sCD163 was almost equal in the respective sera. Concentrations of sCD163 were not affected when passing the liver excluding substantial hepatic removal/release of this protein. A high concentration of IL-6 upregulated CD163 protein while physiological doses had no effect. However, sCD163 was not increased by any of the IL-6 doses tested. FFA even modestly decreased CD163 and sCD163. The anti-inflammatory mediators fenofibrate, pioglitazone, and eicosapentaenoic acid (EPA) did not influence sCD163 levels while CD163 was reduced by EPA. These data suggest that in humans neither visceral fat nor fatty liver are major sources of sCD163.

Fatty acids and hypolipidemic drugs regulate peroxisome proliferator-activated receptors α- and γ-mediated gene expression via liver fatty acid binding protein: A signaling path to the nucleus

Peroxisome proliferator-activated receptor α (PPARα) is a key regulator of lipid homeostasis in hepatocytes and target for fatty acids and hypolipidemic drugs. How these signaling molecules reach the nuclear receptor is not known; however, similarities in ligand specificity suggest the liver fatty acid binding protein (L-FABP) as a possible candidate. In localization studies using laser-scanning microscopy, we show that L-FABP and PPARα colocalize in the nucleus of mouse primary hepatocytes. Furthermore, we demonstrate by pull-down assay and immunocoprecipitation that L-FABP interacts directly with PPARα. In a cell biological approach with the aid of a mammalian two-hybrid system, we provide evidence that L-FABP interacts with PPARα and PPARγ but not with PPARβ and retinoid X receptor-α by protein–protein contacts. In addition, we demonstrate that the observed interaction of both proteins is independent of ligand binding. Final and quantitative proof for L-FABP mediation was obtained in transactivation assays upon incubation of transiently and stably transfected HepG2 cells with saturated, monounsaturated, and polyunsaturated fatty acids as well as with hypolipidemic drugs. With all ligands applied, we observed strict correlation of PPARα and PPARγ transactivation with intracellular concentrations of L-FABP. This correlation constitutes a nucleus-directed signaling by fatty acids and hypolipidemic drugs where L-FABP acts as a cytosolic gateway for these PPARα and PPARγ agonists. Thus, L-FABP and the respective PPARs could serve as targets for nutrients and drugs to affect expression of PPAR-sensitive genes.

Effect of dietary supplementation of tocoferol acetate alone and with varying combinations on growth, survival and fatty acids profile of Macrobrachium rosenbergii larvae through Moina micrura enrichment

A study was carried out to determine the effect of tocopherol acetate along with cod liver oil astaxanthin enriched Moina micrura (MC- control, Ml- tocopherol acetate enriched, M2-tocopherol acetate combined with cod liver oil (CLO) enriched and M3- tocopherol acetate combined with astaxanthin enriched) on growth, survival and fatty acid composition of M. rosenbergii (de Man) larvae (TC- unenriched Moina fed larvae, Tl- tocopherol acetate enriched Moina fed larvae, T2- tocopherol acetate + CLO enriched Moina fed larvae to T3 – tocopherol acetate+ astaxanthin enriched Moina fed larvae). Growth was expressed as the time taken in to the settlement of 95% post larvae. Maximum growth i.e., the lowest time taken to the 95% PL settlement (40 days) and the maximum survival percentage (61%) was observed in both T2 and T3 treatments fed with M2 and M3 Moina respectively. Minimum growth and survival was observed in unenriched Moina fed larvae (TC). In larval treatments T2, (larvae fed with (M2) vitamin E + CLO enriched Moina), showed a higher percentage of EPA, DHA and higher HUFA level than other treatments.

The Peroxisomal Enzyme L-PBE Is Required to Prevent the Dietary Toxicity of Medium-Chain Fatty Acids.

Specific metabolic pathways are activated by different nutrients to adapt the organism to available resources. Although essential, these mechanisms are incompletely defined. Here, we report that medium-chain fatty acids contained in coconut oil, a major source of dietary fat, induce the liver ω-oxidation genes Cyp4a10 and Cyp4a14 to increase the production of dicarboxylic fatty acids. Furthermore, these activate all ω- and β-oxidation pathways through peroxisome proliferator activated receptor (PPAR) α and PPARγ, an activation loop normally kept under control by dicarboxylic fatty acid degradation by the peroxisomal enzyme L-PBE. Indeed, L-pbe(-/-) mice fed coconut oil overaccumulate dicarboxylic fatty acids, which activate all fatty acid oxidation pathways and lead to liver inflammation, fibrosis, and death. Thus, the correct homeostasis of dicarboxylic fatty acids is a means to regulate the efficient utilization of ingested medium-chain fatty acids, and its deregulation exemplifies the intricate relationship between impaired metabolism and inflammation.

Pretranslational regulation of the expression of the lipoprotein lipase (EC 3.1, l.34) gene by dietary fatty acids in the rat

Although there have been a number of studies of effects of diet and hormones on lipoprotein lipase (EC 3.1.1.34; LPL) activity and levels of LPL mRNA (Raynolds et al. 1990), there have been no studies which have investigated effects of different dietary fatty acids on LPL gene expression. In the present study male Wistar Albino rats were pair-fed diets containing 50 g fat/kg of different fatty acid composition for 2 weeks. The diets fed were (1) a mixed oil (450 g saturated fatty acids, 420 g monounsaturated fatty acids, 130 g polyunsaturated fatty acids/kg; n 8), (2) maize oil (n 8), or (3) fish oil (n 8). Animals were killed, RNA was extracted from liver and perirenal and epididymal fat pads, and analysed by ‘Northern methodology’. Samples were hybridized to a human cDNA probe for LPL (Gotoda et al. 1989). Two transcripts were identified in epididymai and perirenal adipose tissue which were approximately 3·7 and 1·7 kb in size. The results suggested that (1) fish oil-fed animals had significantly greater production of LPL mRNA in epididymai adipose tissue compared with maize oil-fed animals (P < 0·05), (2) maize oil-fed animals had significantly greater production of LPL mRNA in perirenal fat compared with the other dietary groups (P < 0·05), (3) expression in the liver was not significant. Rats fed on a fish oil diet had significantly reduced plasma triacylglycerol concentrations compared with the mixed-oil group (P < 0·05), but there were no significant differences in plasma cholesterol. The differences in LPL could not be explained directly by the changes in plasma immunoreactive-insulin and glucose-dependent insulinotrophic polypeptide levels in the three groups.

Fatty acids as trophic biomarkers in vitellogenic females in an impounded tropical river

Fatty acids have been used in marine biogeochemistry as food chain biomarkers, but in freshwater these studies are rare. In order to evaluate the fatty acid potential as biomarkers in freshwater, their profile was analyzed during vitellogenesis in two fish species, in both waterfall and reservoir environments of the Paraiba do Sul River Basin. Detrivorous Hypostomus affinis and omnivorous Geophagus brasiliensis seem to elongate and desaturate polyunsaturated fatty acids (PUFA) and transfer them to the ovaries` phospholipids. Waterfall Geophagus brasiliensis have more highly unsaturated fatty acids in the liver, but in the reservoir, accumulation mainly occurs in muscle and ovary triglycerides, suggesting trophic opportunism and a plasticity during vitellogenesis. In Hypostomus affinis, PUFA alteration occurs only in the reservoir, suggesting a high phytoplankton occurrence. Eutrophication and water speed is reflected in Hypostomus affinis ovaries by higher PUFAn3 and bacterial fatty acids. As in marine environments, analysis of mono- and polyunsaturated fatty acids during vitellogenesis can be used as a tool in food chain studies in freshwater.

N-3 fatty acids and cardiovascular prevention

In this study we elucidate the role of polyunsaturated fatty acids (PUFAs) in the prevention of cardiovascular diseases, focusing the attention on their role in the modulation of acyl composition of cell lipids and of gene expression. Regarding this latter mechanism, the effectiveness of PUFAs as activators of two transcriptional factors, SREBPs and PPARs, have been considered. Two different model system have been used: primary cultures of neonatal rat cardiomyocytes and an human hepatoma cell line (HepG2). Cells have been supplemented with different PUFAs at physiological concentration, and special attention has been devoted to the main n-3 PUFAs, EPA and DHA. PUFAs influence on global gene expression in cardiomyocytes has been evaluated using microarray technique. Furthermore, since it is not fully elucidated which transcription factors are involved in this modulation in the heart, expression and activation of the three different PPAR isoforms have been investigated. Hepatocytes have been used as experimental model system in the evaluation of PUFAs effect on SREBP activity. SREBPs are considered the main regulator of cholesterol and triglyceride synthesis, which occur mainly in the liver. In both experimental models the modification of cell lipid fatty acid composition subsequent to PUFAs supplementation has been evaluated, and related to the effects observed at molecular level. The global vision given by the obtained results may be important for addressing new researches and be useful to educators and policy makers in setting recommendations for reaching optimal health through good nutrition.

Unsaturated fatty acids inhibit transcription of the sterol regulatory element-binding protein-1c (SREBP-1c) gene by antagonizing ligand-dependent activation of the LXR

Sterol regulatory element-binding protein-1c (SREBP-1c) enhances transcription of genes encoding enzymes of unsaturated fatty acid biosynthesis in liver. SREBP-1c mRNA is known to increase when cells are treated with agonists of liver X receptor (LXR), a nuclear hormone receptor, and to decrease when cells are treated with unsaturated fatty acids, the end products of SREBP-1c action. Here we show that unsaturated fatty acids lower SREBP-1c mRNA levels in part by antagonizing the actions of LXR. In cultured rat hepatoma cells, arachidonic acid and other fatty acids competitively inhibited activation of the endogenous SREBP-1c gene by an LXR ligand. Arachidonate also blocked the activation of a synthetic LXR-dependent promoter in transfected human embryonic kidney-293 cells. In vitro, arachidonate and other unsaturated fatty acids competitively blocked activation of LXR, as reflected by a fluorescence polarization assay that measures ligand-dependent binding of LXR to a peptide derived from a coactivator. These data offer a potential mechanism that partially explains the long-known ability of dietary unsaturated fatty acids to decrease the synthesis and secretion of fatty acids and triglycerides in livers of humans and other animals.

Effect of fatty acids, glucose, and insulin on hepatic glucose uptake and glycolysis

Objective:. There is evidence from in vitro studies that fatty acids can inhibit glucose uptake in liver. However, it is uncertain whether this happens in vivo when the liver is exposed to high levels of glucose and insulin, in combination with fatty acids, after a mixed meal. This study determined the effects of a combination of fatty acids and insulin on glucokinase (GK) activity and glycolysis in primary rat hepatocytes. Methods: Hepatocytes were cultured with 15 mM glucose and 2 or 10 nM insulin in combination with the fatty acids palmitate, oleate, linoleate, eicosapentaenoic acid, or docosahexaenoic acid. Total GK activity and the proportion of GK in the,active, unbound state were measured to determine the effect of fatty acid on the activity and cellular localization of GK. Glucose phosphorylation and glycolysis were measured in intact cells. Lactate and pyruvate synthesis and the accumulation of ketone bodies were also estimated. Results: Palmitate and eicosapentaenoic acid lowered total GK activity in the presence of 2 nM insulin, but not with 10 nM insulin. In contrast, oleate, linoleate, and docosahexaenoic acid did not alter GK activity. None of the fatty acids tested inhibited glucose phosphorylation or glycolysis in intact rat hepatocytes. In addition, GK activity was unaffected by insulin concentration. Conclusion: Some fatty acids can act to inhibit GK activity in primary hepatocytes. However, there was no,evidence that this decrease in GK activity impaired glucose phosphorylation or glycolysis. Glucose and high concentrations of insulin, which promote glucose uptake, appear to counteract any inhibitory action of fatty acids. Therefore, the presence of fatty acids in a normal mixed meal is likely to have little effect on the capacity of the liver to take up, phosphorylate, and oxidize glucose. (C) 2006 Elsevier Inc. All rights reserved.

Deleterious Effects of Lard-enriched Diet on Tissues Fatty Acids Composition and Hypothalamic Insulin Actions

Altered tissue fatty acid (FA) composition may affect mechanisms involved in the control of energy homeostasis, including central insulin actions. In rats fed either standard chow or a lard-enriched chow (high in saturated/low in polyunsaturated FA, HS-LP) for eight weeks, we examined the FA composition of blood, hypothalamus, liver, and retroperitoneal, epididymal and mesenteric adipose tissues. Insulin-induced hypophagia and hypothalamic signaling were evaluated after intracerebroventricular insulin injection. HS-LP feeding increased saturated FA content in adipose tissues and serum while it decreased polyunsaturated FA content of adipose tissues, serum, and liver. Hypothalamic C20:5n-3 and C20:3n-6 contents increased while monounsaturated FA content decreased. HS-LP rats showed hyperglycemia, impaired insulin-induced hypophagia and hypothalamic insulin signaling. The results showed that, upon HS-LP feeding, peripheral tissues underwent potentially deleterious alterations in their FA composition, whist the hypothalamus was relatively preserved. However, hypothalamic insulin signaling and hypophagia were drastically impaired. These findings suggest that impairment of hypothalamic insulin actions by HS-LP feeding was not related to tissue FA composition.

Long Chain Saturated Fatty Acids Increase Haptoglobin Gene Expression in C57BL/6J Mice Adipose Tissue and 3T3-L1 Cells

Background Dietary lipids are directly related to the composition of adipose tissue, aetiology of obesity and arousal of obesity-related pathologies, like chronic inflammation states. Haptoglobin is an acute phase protein secreted by the liver and white adipose tissue, and its blood levels vary according to the volume of fat in the body. Aim of the study To investigate the effect of diets enriched with large amounts of dietary fats, which differ in their fatty acid composition, on the haptoglobin gene expression by visceral and subcutaneous adipose tissue of mice fed for 2 days or 8 weeks. 3T3-L1 cells were treated with fatty acids that are found in those types of dietary fats. Methods Mice were treated acutely (for 2 days) or chronically (for 8 weeks) with diets enriched with soybean oil, fish oil, coconut oil or lard. 3T3-L1 cells were treated with six different fatty acids. Haptoglobin gene expression was quantified by northern blotting. Results Both chronic and acute treatment with lard, which is rich in long chain saturated fatty acids, increased the haptoglobin mRNA expression in the retroperitoneal and epidydimal white adipose tissues. Chronic treatment with coconut oil, which is rich in medium chain saturated fatty acids, increased the haptoglobin expression in the epidydimal and subcutaneous depots. In 3T3-L1, palmitic acid increased the haptoglobin gene expression. Conclusion The type of lipids in the diet can differently modulate the white adipose tissue gene expression of haptoglobin, and saturated fatty acids play a major role in promoting a pro-inflammatory environment. This response is fat pad specific and dependant on the duration of treatment.