Effect Of PUFA Research Articles

Polyphenol supplementation ameliorates PUFA benefits in metabolic and oxidative status in dogs

The effect of PUFA on obesity‐associated oxidant stress could be explained by the stimulation of endogenous antioxidant processes, or by their own ability to be oxidized. The adjunction of antioxidant to PUFA could help to elucidate their mechanism of action.Our aim was to check the effects of PUFA supplementation w/wo curcumin polyphenols on metabolic status, plasma lipids, and antioxidant status in dogs.Obese dogs were given for 2 consecutive periods of 6 w hyperenergetic diet supplemented with either n‐3 PUFA (Diet1) then n‐3 PUFA plus curcumin (Diet2). Before (T0) and at the end of each 6‐wk period, body composition, insulin sensitivity (IS), plasma lipid and oxidative status markers (total antioxidant status, TAS and glutathione peroxidise, GPx) were determined.At the end of both periods, body composition and IS were did not differ from T0 values. At the end of Diet1, plasma NEFA were lower and total cholesterol was higher than at T0; at the end of Diet2, TG levels were lower. The TAS was higher than at T0 at the end of Diet1, and even more at the end of Diet2. Compared to T0 GPx activity was unchanged at the end of each period.Our results show that polyphenols could have synergistic effects with PUFA. This suggests that PUFA would not act as oxidation substrates. Indeed their protection against oxidation would account for their action. Further experiments could be helpful for a better understanding of the mechanism of action.

Abstract TP106: N-3 Polyunsaturated Fatty Acid Enhances Neurovascular Remodeling After Acute Cerebral Ischemia

INTRODUCTION: Ischemic stroke triggers multiple repair responses, including neurogenesis, angiogenesis and oligodendrogenesis. These endogenous processes, however, are insufficient for effective brain repair. Our previous study has shown that omega-3 polyunsaturated fatty acid (N3 PUFA) is a potential neurogenic treatment for stroke recovery. The effect of N3 PUFA on revasularization and white matter recovery, however, remains unexplored. HYPOTHESIS: N3 PUFA enhances revasularization and white matter recovery after ischemic stroke, leading to long-term neurological recovery. METHODS: Mice were treated with N3 PUFA-enriched diet or regular diet for 3 months and then subjected to MCAO for 60 minutes. Brdu was administered to label newly generated cells. Animals were sacrificed on day 1, 3, 7, 14 or 35 of reperfusion. Functional vessels were identified by transcardial perfusion of FITC-conjugated tomato lectin , which labels endothelial cells only in perfused vessels. White matter integrity was evaluated by immunohistochemistry staining of myelin basic protein (MBP), SMI32 and neurofilament (NF) 200. RESULTS: The vascular reperfusion in the ischemic core and penumbra was preserved in N3 PUFA-supplemented mice since 1 day after MCAO and maintained significantly higher than regular diet group up to 35 days post-injury. Angiogenesis was enhanced by N3 PUFA, as revealed by substantially increased double staining of Brdu with tomato lectin at 7-35 days after MCAO. Importantly, clusters of DCX+ immature neurons localized proximal to revascularized vessels beginning 14 days after ischemia, suggesting interplay between revascularization and neurogenesis. Post-stroke white matter injury was also ameliorated by N3 PUFA, as revealed by enhanced MBP staining for mature myelin and reduced SMI32 staining for abnormally dephosphorylated neurofilament. Meanwhile, axon integrity was markedly preserved in N3 PUFA-treated mice. As a result, N3 PUFA supplementation significantly reduced the infarct volume, which was accompanied by improved neurological functions up to 35 days after reperfusion.

Fatty acids do not pay the toll: effect of SFA and PUFA on human adipose tissue and mature adipocytes inflammation

BackgroundOn the basis that high fat diet induces inflammation in adipose tissue, we wanted to test the effect of dietary saturated and polysunsaturated fatty acids on human adipose tissue and adipocytes inflammation. Moreover we wanted to determine if TLR2 and TLR4 are involved in this pathway.MethodsHuman adipose tissue and adipocytes primary cultures were treated with endotoxin-free BSA conjugated with SFA (lauric acid and palmitic acid - LA and PA) and PUFA (eicosapentaeneic acid, docosahexaenoic acid and oleic acid - EPA, DHA and OA) with or without LPS. Cytokines were then assayed by ELISA (TNF-alpha, IL-6 and MCP-1). In order to determine if TLR2 and TLR4 are activated by fatty acid (FA), we used HEK-Blue cells transfected by genes from TLR2 or TLR4 pathways associated with secreted alkaline phosphatase reporter gene.ResultsNone of the FA tested in HEK-Blue cells were able to activate TLR2 or TLR4, which is concordant with the fact that after FA treatment, adipose tissue and adipocytes cytokines levels remain the same as controls. However, all the PUFA tested: DHA, EPA and to a lesser extent OA down-regulated TNF-alpha, IL-6 and MCP-1 secretion in human adipose tissue and adipocytes cultures.ConclusionsThis study first confirms that FA do not activate TLR2 and TLR4. Moreover by using endotoxin-free BSA, both SFA and PUFA tested were not proinflammatory in human adipose tissue and adipocytes model. More interestingly we showed that some PUFA exert an anti-inflammatory action in human adipose tissue and adipocytes model. These results are important since they clarify the relationship between dietary fatty acids and inflammation linked to obesity.

Myocardial infarction in relation to mercury and fatty acids from fish: a risk-benefit analysis based on pooled Finnish and Swedish data in men

Exposure to methylmercury from fish has been associated with increased risk of myocardial infarction (MI) in some studies. At the same time, marine n-3 (omega-3) PUFAs are an inherent constituent of fish and are regarded as beneficial. To our knowledge, no risk-benefit model on the basis of data on methylmercury, PUFA, and MI risk has yet been presented. The objective of this study was to describe how exposure to both marine n-3 PUFAs and methylmercury relates to MI risk by using data from Finland and Sweden. We used matched case-control sets from Sweden and Finland that were nested in population-based, prospective cohort studies. We included 361 men with MI from Sweden and 211 men with MI from Finland. MI risk was estimated in a logistic regression model with the amount of mercury in hair (hair-Hg) and concentrations of n-3 PUFAs (EPA and DHA) in serum (S-PUFA) as independent variables. The median hair-Hg was 0.57 μg/g in Swedish and 1.32 μg/g in Finnish control subjects, whereas the percentage of S-PUFA was 4.21% and 3.83%, respectively. In combined analysis, hair-Hg was associated with higher (P = 0.005) and S-PUFA with lower (P = 0.011) MI risk. Our model indicated that even a small change in fish consumption (ie, by increasing S-PUFA by 1%) would prevent 7% of MIs, despite a small increase in mercury exposure. However, at a high hair-Hg, the modeled beneficial effect of PUFA on MI risk was counteracted by methylmercury. Exposure to methylmercury was associated with increased risk of MI, and higher S-PUFA concentrations were associated with decreased risk of MI. Thus, MI risk may be reduced by the consumption of fish high in PUFAs and low in methylmercury.

The effect of EPA and DHA on metabolic syndrome patients: a systematic review of randomised controlled trials

Metabolic syndrome (MS) is characterised by accumulation of CVD risk factors. The use of very long chain n-3 polyunsaturated fatty acids (VLC n3 PUFA) could potentially benefit MS by reducing risk factors. To better understand the possible VLC n3 PUFA benefits, the literature was systematically reviewed for randomised controlled trials (RCT) that published effects of VLC n3 PUFA on MS patients. 17 RCT fulfilled the inclusion criteria and were analysed for relevance to the research question. The available RCT convincingly show that the administration of VLC n3 PUFA doses > 1 g for at least 3 months produces a significant reduction of triglycerides ranging from 7 % to 25 %. These results confirm the hypotriglyceridemic effect of VLC n3 PUFA in MS patients. The triglyceride lowering may produce further benefits by reducing the % of pro-atherogenic small dense LDL particles (sdLDL) and also perhaps by ameliorating the inflammatory process associated with MS. High doses of VLC n3 PUFA ( ≥ 3 g/day) may produce further TAG reductions but could raise other risk factors such as LDL-C. No clear effects were found on other MS markers. The combination of VLC n3 PUFA plus a statin may be useful to prevent the occurrence of coronary events. More studies are needed using different amounts of VLC n3 PUFA, time lengths, dietary backgrounds and different profiles of MS patients before clear recommendations can be made.

Effect of ω3 PUFA on diet induced non‐alcoholic fatty liver disease (NAFLD) development and progression in C57BL/6J mice

The incidence of NAFLD and non‐alcoholic steatohepatitis (NASH) has increased in parallel with obesity. While both are characterized by excessive hepatic lipid accumulation, NASH is defined as hepatic inflammation with hepatocellular damage. Our goal was to examine the effect of C20–22 ω3 PUFA on diet induced NASH in LDLR−/− C57BL/6J mice. Mice consumed the Western Diet (WD) supplemented with olive oil, eicosapentaenoic acid (20:5ω3; EPA), docosahexaenoic acid (22:6 ω3; DHA) or both EPA and DHA for 16 weeks. The WD induced a severe phenotype similar to human NASH; including robust induction of hepatosteatosis, inflammation (MCP1) and fibrosis (ProCol1α1). While dietary C20–22 ω3 PUFA failed to suppress hepatic steatosis, ω3 PUFA attenuated markers of inflammation, fibrosis, and liver damage (plasma ALT, AST). The ω3 PUFA effect on inflammation & fibrosis correlated with the down regulation of multiple transcripts involved in toll‐like receptor signaling (TRL2, TRL4, CD14). Moreover, DHA was significantly more effective than EPA or the combination of EPA & DHA at suppressing markers of inflammation and fibrosis associated with NASH. Thus, dietary ω3 PUFA attenuates inflammation & fibrosis without suppressing hepatic lipid.Research Support: USDA Grant 2009‐65200‐05846

Chronic dietary intake of α-linolenic acid does not replicate the effects of DHA on passive properties of entorhinal cortex neurons

n-3 PUFA are receiving growing attention for their therapeutic potential in central nervous system (CNS) disorders. We have recently shown that long-term treatment with DHA alters the physiology of entorhinal cortex (EC) neurons. In the present study, we investigated by patch-clamp the effect of another major dietary n-3 PUFA, α-linolenic acid (LNA), on the intrinsic properties of EC neurons. Mice were chronically exposed to isoenergetic diets deficient in n-3 PUFA or enriched in either DHA or LNA on an equimolar basis. GC analyses revealed an increase in DHA (34%) and a decrease in arachidonic acid (AA, - 23%) in brain fatty acid concentrations after consumption of the DHA-enriched diet. Dietary intake of LNA similarly affected brain fatty acid profiles, but at a lower magnitude (DHA: 23%, AA: - 13%). Compared to the n-3 PUFA-deficient diet, consumption of DHA, but not LNA, induced membrane hyperpolarisation ( -60 to -70 mV), increased cellular capacitance (32%) and spontaneous excitatory postsynaptic current frequency (50%). We propose that the inefficiency of LNA to modulate cellular capacitance was related to its inability to increase the brain DHA:AA ratio over the threshold necessary to up-regulate syntaxin-3 (46%) and translocate drebrin (40% membrane:cytosol ratio). In summary, our present study shows that the increase in brain DHA content following chronic administration of LNA was not sufficient to alter the passive and synaptic properties of EC neurons, compared to direct dietary intake of DHA. These diverging results have important implications for the therapeutic use of n-3 PUFA in CNS disease, favouring the use of preformed DHA.

Effect of PUFA on embryo cryoresistance, gene expression and AMPKα phosphorylation in IVF-derived bovine embryos

The objectives of the present study were to evaluate the effect of conjugated linoleic acid (CLA t10, c12, C18:2), linolenic acid (C18:3) and docosahexaenoic acid (DHA, C22:6) supplementation on in vitro bovine embryo development, embryo survival after cryopreservation, gene expression and AMPKα phosphorylation. Control groups with modified synthetic oviduct fluid (mSOF) ± 100 μM β-mercaptoethanol (β-ME) were performed. The effects of co-culture with bovine oviduct epithelial cell (Boec) monolayers, serum supplementation and embryo development in the ewe oviduct, on gene expression were also examined. Experiments 1 and 2: a lower d 7 embryo survival was found with 100 μM C22:6 and 100 μM C18:2 supplementation compared to 1 μM C22:6 and 100 μM β-ME supplementation ( P < 0.05). C18:3 supplementation had no effect on d 7 embryo survival, but 100 μM C18:3 increased d 8 embryo survival compared to 100 μM β-ME supplementation ( P < 0.05). Experiments 3 and 4: stearoyl-CoA desaturase 1 (SCD1) and sterol regulatory element-binding transcription factor 1 (SREBP1) mRNA decreased after 10 μM C22:6 supplementation compared to all other supplementations ( P < 0.05). A lower fatty acid desaturase 2 (FADS2) transcript level was found with 100 μM C18:2, 10 μM C22:6 and 10 μM C18:3 supplementations compared to groups without fatty acid supplementation ( P < 0.05). Acetyl-CoA-carboxylase (ACC), fatty acid synthase (FAS), adipose differentiation-related protein (ADRP), acyl-CoA synthetase long-chain family member 1 (ACSL1), diacylglycerol O-acyltransferase 1 (DGAT1), carnitin palmitoyltransferase-II (CPT-II) mRNAs expression and AMPKα phosphorylation were not modified with PUFA supplementation. Experiment 5: SCD1 and FAS mRNA decrease in Boec group compared to serum supplementation, as SCD1 mRNA in ewe oviduct group ( P < 0.05). In conclusion, this study showed that a PUFA supplementation with C18:2, C18:3 or C22:6 in bovine culture development for 6 days and co-culture with Boec down-regulate mRNA expression of proteins involved in lipid metabolism in d 7–8 embryo (SCD1 and FADS2 desaturases), probably through SREBP1 mRNA regulation after 10 μM C22:6 supplementation, indicating a modification of saturated/unsaturated fatty acid balance in bovine blastocyst.

N-3 andn-6 Polyunsaturated fatty acids suppress sterol regulatory element binding protein activity and increase flow of non-esterified cholesterol in HepG2 cells

The plasma lipid-lowering effect of PUFA, one of their main beneficial effects, is considered to be related to the regulation of lipid biosynthesis through transcription factors including sterol regulatory element binding proteins (SREBP). In the present study, we compared the effect of different PUFA on SREBP activity in HepG2 cells, using a sterol regulatory element-luciferase reporter construct as a probe. Supplementation with different fatty acids reduced SREBP activity in the order 20 : 5n-3 = 18 : 2n-6 = 20 : 4n-6 " 18 : 3n-3 = 22 : 6n-3 = 22 : 5n-6 " 18 : 1n-9. The suppression of SREBP activity greatly depended on the degree of incorporation of the supplemented PUFA into cellular lipids, and correlated positively with the unsaturation index (r 0.831; P < 0.01) of total cell lipids. Supplemented PUFA were also metabolised to longer and more unsaturated species. These processing activities were higher for n-3 than n-6 PUFA (P < 0.01). We studied the effect of PUFA on the intracellular distribution of non-esterified cholesterol, using filipin staining and fluorescence microscopy with or without the cholesterol traffic blocker U18666A. The data show that the incorporation of PUFA increases non-esterified cholesterol flow from the plasma membrane to intracellular membranes. We conclude that suppression of SREBP activity by PUFA depends on the degree of incorporation into cellular lipids, and is associated with increased flow of non-esterified cholesterol between the plasma membrane and intracellular membranes.

Dietaryn-3 polyunsaturated fatty acids enhance metastatic dissemination of murine T lymphoma cells

Epidemiological investigation and animal studies have shown that dietary n-3 PUFA prevent the development and progression of certain types of cancer. However, conflicting results have been reported by the few studies that focused on the effect of dietary n-3 PUFA on the development of metastases. In the present study, we investigated the metastatic dissemination of murine T lymphoma lines with different metastatic potential transplanted into mice fed a fish oil diet, compared with mice fed a maize oil diet. Transplantation of highly metastatic S11 cells into animals fed a fish oil diet induced a large lymphomatoid infiltration in the spleen, associated with an eight-fold increase in spleen weight, compared with normal animals on the same diet. In contrast, only a limited increase in spleen weight was found in animals transplanted with S11 cells while fed a maize oil diet. No significant increase in spleen weight was found in animals transplanted with low-metastatic 164T2 cells regardless of whether they were fed a fish oil or a maize oil diet. At the end of experiment, an overt cachexia was shown by animals fed a fish oil diet transplanted with S11 cells, but not by those transplanted with 164T2 cells. The particularly high pro-metastatic effect of dietary n-3 PUFA on S11 cells rules out the generalisation that dietary n-3 PUFA inhibit tumour growth and progression.

An enhanced apoptosis and a reduced angiogenesis are associated with the inhibition of lung colonisation in animals fed ann-3 polyunsaturated fatty acid-rich diet injected with a highly metastatic murine melanoma line

Both epidemiological and experimental studies indicate that dietary n-3 PUFA inhibit carcinogenesis and tumour growth. Metastatic diffusion has also been found to be affected in animals fed diets containing purified n-3 PUFA or fish oil. In the present study, we investigated whether the metastatic diffusion of a highly metastatic variant (F10-SR cells) isolated from the B16 melanoma F10 line was affected by feeding host animals a diet containing 5 % fish oil. In these animals, compared with those fed a diet containing 5 % maize oil, there was a reduced number of metastatic pulmonary colonies. The immunohistochemical analysis of appropriate markers revealed that the antimetastatic effect of dietary n-3 PUFA was not related to a reduction of proliferation, but rather to an enhanced apoptotic activity. The reduction of von Willebrand factor immunoreactivity found in pulmonary colonies of F10-SR cells grown in fish oil-fed animals indicates that a decrease of angiogenesis contributes to the antimetastatic effect of dietary n-3 PUFA. This conclusion stands in spite of the higher expression of vascular endothelial growth factor observed in pulmonary colonies grown in fish oil-fed animals.

Dietary supplementation with ω-3 PUFA increases adiponectin and attenuates ventricular remodeling and dysfunction with pressure overload

Epidemiological studies suggest that consumption of omega-3 polyunsaturated fatty acids (omega-3 PUFA) decreases the risk of heart failure. We assessed the effects of dietary supplementation with omega-3 PUFA from fish oil on the response of the left ventricle (LV) to arterial pressure overload. Male Wistar rats were fed a standard chow or a omega-3 PUFA-supplemented diet. After 1 week rats underwent abdominal aortic banding or sham surgery (n=9-12/group). LV function was assessed by echocardiography after 8 weeks. In addition, we studied the effect of omega-3 PUFA on the cardioprotective adipocyte-derived hormone adiponectin, which may alter the pro-growth serine-threonine kinase Akt. Banding increased LV mass to a greater extent with the standard chow (31%) than with omega-3 PUFA (18%). LV end diastolic and systolic volumes were increased by 19% and 105% with standard chow, respectively, but were unchanged with omega-3 PUFA. The expression of adiponectin was up-regulated in adipose tissue, and the plasma adiponectin concentration was significantly elevated. Treatment with omega-3 PUFA increased total Akt protein expression in the heart, but decreased the fraction of Akt in the active phosphorylated form, and thus did not alter the amount of active phospho-Akt. Dietary supplementation with omega-3 PUFA attenuated pressure overload-induced LV dysfunction, which was associated with elevated plasma adiponectin.

Protective effect of n-3 polyunsaturated fatty acids concentrate on isoproterenol-induced myocardial infarction in rats

The protective effect of PUFA concentrate prepared from fish oil on isoproterenol-induced myocardial infarction in male albino rats was investigated with respect to changes in the levels of diagnostic marker enzymes, cholesterol, triglycerides, free fatty acids, phospholipids, reduced glutathione (GSH) and lipid peroxides (LPO). Administration of PUFA concentrate significantly prevented the isoproterenol-induced elevation in the levels of plasma diagnostic marker enzymes (ALT [93.5%], AST [95.6%], LDH [94.7%] and CPK [96.1%]). PUFA concentrate feeding exerted a significant antilipidemic effect against isoproterenol-induced myocardial infarction by reducing the levels of lipid components in plasma (cholesterol [71.5%], triglycerides [79.7%] and free fatty acids [70.7%] and heart tissue (cholesterol [81.4%], triglycerides [76.3%] and free fatty acids [78.6%]). A tendency to prevent the isoproterenol-induced phospholipids depletion (74.4%) in the myocardium of experimental rats was also observed. The level of lipid peroxidation was also found to be significantly lower in PUFA treated animals (2.72±0.15 nmol/ml in plasma; 1.18±0.08 nmol/mg protein in heart tissue) as compared to that of isoproterenol-injected groups (5.77±0.43 nmol/ml in plasma; 2.14±0.15 nmol/mg protein in heart tissue) of rats. Also the level of reduced GSH significantly higher in the heart tissue of PUFA administered experimental rats (5.65±0.98 μg/g) as compared to myocardial infarction induced control rats (2.39±0.18 μg/g). The results of the present study indicate that the overall cardioprotective effect of PUFA concentrate is probably related to its ability to inhibit lipid accumulation by its hypolipidaemic property.

Th-W53:7 Effect of omega-3 PUFA on carotid IMT and haemostasis in hypertrigly ceridemic patients: A longitudinal pilot study in primary prevention

Th-W53:7 Effect of omega-3 PUFA on carotid IMT and haemostasis in hypertrigly ceridemic patients: A longitudinal pilot study in primary prevention

We-P12:305 Porphyromonas gingivalis induces platelet aggregation and blood coagulation — role of gingipains and lipopolysaccharides

Although several investigations have linked the degree of fatty acid saturation to plasma lipid responses in the postprandial state, further evaluation is necessary. In this study, we compared the effect of saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids on postprandial lipid metabolism using complementary in vivo and in vitro approaches. Fat (10 g) cholesterol (0.5 g) test meals that provided either lard (SFA), olive oil (MUFA), or sunflower oil (PUFA) were ingested by chow-fed New Zealand white rabbits (n = 8). In addition, hepatic uptake of triglyceride-cholesterol-rich lipoproteins (TCRL) isolated from rabbits chronically ingesting SFA, MUFA, or PUFA diets was measured using freshly isolated chow-fed rabbit hepatocytes. Whatever dietary fatty acids ingested, postprandial triglyceridemia and occurrence of radiolabelled dietary lipids in plasma were not markedly different. Conversely, SFA induced higher postprandial cholesterolemia and phospholipemia than MUFA (P < 0.05) whereas PUFA prevented postprandial cholesterol increase. TCRL disappearance from cultured liver cell media was delayed with SFA-rich TCRL and faster with PUFA whereas MUFA-rich TCRL showed an intermediate figure. From these data, we conclude that SFA, MUFA, and PUFA elicited different postprandial plasma and lipoprotein lipid responses. The fatty acid composition of TCRL had a major impact on their subsequent metabolism, especially uptake by cultured hepatocytes. The SFA-induced hypercholesterolemia could be related to an altered hepatic uptake whereas a faster clearance and hepatic uptake could explain the cholesterol-lowering effect of PUFA in rabbits. MUFA, like PUFA, accelerate uptake by hepatocytes but favor cholesterol ester enrichment of TCRL.

Dietary (n-3) Polyunsaturated Fatty Acids Inhibit HER-2/neu-Induced Breast Cancer in Mice Independently of the PPARγ Ligand Rosiglitazone

Overexpression of human epidermal growth factor receptor 2 (HER-2/neu) characterizes a molecular subtype of breast cancer associated with poor clinical outcome. Preventive strategies for HER-2/neu-positive breast cancer, which is often estrogen and progesterone receptor negative, remain undefined. Activators of peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear hormone receptor also expressed in breast cancer, hold potential as cancer prevention agents. PPARgamma ligands include specific fatty acids and synthetic compounds, such as the thiazolidinediones, which appear to inhibit cell proliferation and tumorigenesis. We hypothesized that a thiazolidinedione, rosiglitazone, may serve as a chemopreventive agent for HER-2/neu-associated mammary carcinogenesis, but that efficacy may be influenced by dietary fat content. We studied the effects of diets enriched with corn or fish oil (25% of energy) with and without rosiglitazone (12 g/kg) in a 2 x 2 factorial design on mammary tumorigenesis in murine mammary tumor virus (MMTV)-HER-2/neu transgenic mice. Despite in vitro evidence of antiproliferative effects in an MMTV-HER-2/neu tumor cell line, rosiglitazone did not affect mammary carcinogenesis in vivo. Interestingly, fish oil-based diets markedly suppressed breast tumor incidence (57% of mice vs. 87% of corn oil-fed mice, P = 0.0001) as well as tumor multiplicity (P = 0.001) and mammary gland dysplasia (P = 0.001). These findings demonstrate a potent preventive effect of (n-3) PUFA on HER-2/neu-mediated mammary carcinogenesis, without interaction with a synthetic PPARgamma activator. Further studies focusing on the mechanisms by which (n-3) fatty acids suppress HER-2/neu signaling pathways involved in the pathogenesis of breast cancer are warranted.

PENINGKATAN KADAR LEPTIN DENGAN PUFA (Polyunsaturated Fatty Acid) MELALUI AKTIVASI PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR gamma (PPARγ) PADA KULTUR PREADIPOSIT KELINCI

ABSTRACT For the past three decades, PUFA has been recognized as importnant energy sources and cell membrane component. PUFA also plays key roles in many cellular events such as gene regulation and leptin activation. The role of this fatty acid is still unknown especially in vitro. The purpose of this research was to examine the effect of PUFA of the corn oil in increasing leptin concentration by PPARγ activation. Preadipocyte culture from rabbit was incubated by PUFA of corn oil. PUFA have been given on doses 0, 4, 8 and 16 µM. PPARγ protein and leptin levels were analyzed by ELISA. PPARγ expression  was  analyzed  by  immunocytochemistry.  The research  result  showed  that  every  treatment  has  increased PPARγ levels inconsistently. PPARγ concentration increased significantly on 4 µM PUFA treatment compared to control, 8 and 16 µM PUFA of corn oil. But there were no significant difference between control and 8 µM PUFA treatments. Leptin levels increased significantly between administration on 4 µM PUFA and 16 µM PUFA of corn oil administration. Leptin levels was not significantly different between control and 8 µM PUFA. There was also strong correlation between PPARγ expression and leptin levels. PUFA of corn oil increases leptin levels through PPARγ activation. Key words: PUFA, preadipocyte, leptin, PPARγ

Dietaryn-6:n-3 fatty acid ratio in the perinatal period affects bone parameters in adult female rats

PUFA and their metabolites are important regulators of bone formation and resorption. The effect of PUFA on bone growth may be especially striking during the perinatal period. The aim of the present study was to investigate the effect of diets with different n-6:n-3 fatty acid (FA) ratios during the perinatal period on bone parameters in the adult offspring. During late gestation and throughout lactation, rat dams were fed an isoenergetic diet containing 70 g linseed oil (n-3 diet), soyabean oil (n-6+n-3 diet) or sunflower-seed oil (n-6 diet) per kg with n-6:n-3 FA ratios of 0.4, 9 and 216, respectively. The offspring were weaned onto an ordinary chow and followed until 30 weeks of age. Bone parameters were analysed using peripheral quantitative computerised tomography and dual-energy X-ray absorptiometry. Femur length and cortical cross-sectional bone area and bone mineral content were significantly higher in the n-6+n-3 group than in the other groups. Cortical bone thickness in the n-6+n-3 group was increased compared with the n-3 group, but most cortical bone parameters did not differ between the n-3 and n-6 groups. The results suggest that regulatory mechanisms were influenced by the n-6:n-3 FA ratio early in life and not compensated for by the introduction of an ordinary diet after weaning.

Effects of dietary n-3 polyunsaturated fatty acids, breed and dietary vitamin E on the fatty acids of lamb muscle, liver and adipose tissue.

The effect of feeding n-3 PUFA on the fatty acid composition of muscle, adipose tissue and liver of lambs was investigated. Groups of eight ram lambs per breed, SuffolkxLleyn (24 kg live weight) and Scottish Blackface (18 kg live weight), were each fed one of six diets containing one of three fat sources (50 g fatty acids/kg DM; Megalac((R)) (calcium soap of palm fatty acid distillate; Volac Ltd, Royston, Herts., UK) and formaldehyde-treated whole linseed (Trouw Nutrition UK, Northwich, Ches., UK) either alone or with fish oil (1:1, w/w) and either 100 or 500 mg alpha-tocopheryl acetate/kg DM. Feed was offered ad libitum until slaughter at approximately half breed mature live weight. The type of dietary fat had no effect on intake, growth rate or feed conversion ratio. The 3.0-fold higher concentration of 18 : 3n-3 in the linseed compared with the Megalac((R)) diet approximately doubled (P<0.001) the concentration in the neutral and polar lipid fractions of musculus semimembranosus and liver, and in adipose tissue it increased 2.5-fold. Feeding protected linseed also increased (P<0.001) concentrations of 20 : 5n-3 and 22 : 5n-3 in muscle polar lipids and both lipid fractions of liver. The linseed-fish oil raised the 20 : 5n-3 concentrations above those for the linseed diet and also increased 22 : 6n-3. Scottish Blackface lambs had lower concentrations of 18 : 3n-3 in all lipids compared with Suffolk x Lleyn lambs, but more 20 : 5n-3 in the polar lipids of muscle and liver. High levels of dietary vitamin E were associated with small decreases in the concentration of monounsaturated fatty acids and increases in PUFA. Linseed raised the PUFA : saturated fatty acid ratios in liver and adipose tissue but not in muscle, and improved the n-6 : n-3 fatty acid ratio, as did the linseed-fish oil. Different combinations of dietary fatty acids and better protection against rumen biohydrogenation are required to improve muscle PUFA : saturated fatty acids ratios.

Omega-3 polyunsaturated fatty acids inhibit the accumulation of PAS-positive material in the myocardium of STZ-diabetic wistar rats

This study was conducted to investigate the effect of Omega-3 PUFA on streptozotocin (STZ)-induced diabetic cardiomyopathy in wistar rats. After 4 weeks of STZ (60 mg/kg, i.v.) administration, the diabetic animals were randomly divided into two groups: Diabetic control and Omega-3 PUFA treated diabetic rats. Omega-3 PUFA (0.5 ml/kg) was administered to the latter group for 10 weeks. Age matched normal rats served as Normal controls. During the study, plasma glucose, glycosylated hemoglobin, plasma cholesterol, LDL and HDL cholesterol, triglyerides were evaluated in all the groups. Omega-3 PUFA treatment did not normalise but instead blunted the effect of diabetes with regards to the above parameters significantly ( P<0.01). At the end of the experiment, morphometric and histochemical studies were performed on heart and myocardial enzyme markers were studied. In the diabetic control group, diabetic cardiomyopathy was characerised by elevated CPK (DC 110±8.85 vs. NC 39±5.83) and morphological changes in heart. Gravimetric ratios showed increased heart-to-body weight ratio in diabetic control over normal control group. (DC 3.38±0.05 vs. NC 2.48±0.03). Histochemical evidence showed increased accumulation of PAS-positive material in myocardial interstitium (++++). The Omega-3 PUFA treatment blunted all these adverse effects of diabetes on heart significantly ( P<0.001). However, further studies are warranted to elucidate the mechanism by which Omega-3 PUFA decreases the accumulation of PAS-positive material in diabetic myocardium.