RESUMO
PURPOSE: This study was conducted to investigate the effect of fish oil (FO) and krill oil (KO) supplementation on glucose tolerance in obese New Zealand white rabbits. METHODS: The experiments were carried out with 24 male rabbits randomly divided into four groups: KO-castrated, treated with KO; FO-castrated, treated with FO; C-castrated, non-treated; NC-non-castrated, non-treated. At the end of treatment period (2 months), an intravenous glucose tolerance test (IVGTT) was performed in all rabbits. RESULTS: Fasting blood glucose concentrations in FO and KO animals were significantly lower than in group C. The blood glucose concentrations in FO- and KO-treated animals returned to initial values after 30 and 60 min of IVGTT, respectively. In liver, carnitine palmitoyltransferase 2 (Cpt2) and 3-hydroxy-3-methyl-glutaryl-CoA synthase 2 (Hmgcs2) genes were significantly increased in FO-fed rabbits compared with the C group. Acetyl-CoA carboxylase alpha (Acaca) expression was significantly reduced in both KO- and FO-fed rabbits. In skeletal muscle, Hmgcs2 and Cd36 were significantly higher in KO-fed rabbits compared with the C group. Acaca expression was significantly lower in KO- and FO-fed rabbits compared with the C group. CONCLUSION: The present results indicate that FO and KO supplementation decreases fasting blood glucose and improves glucose tolerance in obese New Zealand white rabbits. This could be ascribed to the ameliorated insulin sensitivity and insulin secretion and modified gene expressions of some key enzymes involved in ß-oxidation and lipogenesis in liver and skeletal muscle.
Assuntos
Metabolismo dos Carboidratos/efeitos dos fármacos , Suplementos Nutricionais , Óleos de Peixe/administração & dosagem , Obesidade/sangue , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Animais , Glicemia/metabolismo , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Euphausiacea , Peixes , Regulação da Expressão Gênica , Hidroximetilglutaril-CoA Sintase/genética , Hidroximetilglutaril-CoA Sintase/metabolismo , Insulina/sangue , Resistência à Insulina , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , CoelhosRESUMO
The aim of the study was to explore the effects of 12 weeks daily krill oil supplementation on fasting serum triglyceride (TG) and lipoprotein particle levels in subjects whose habitual fish intake is low and who have borderline high or high fasting serum TG levels (150-499 mg/dL). We hypothesized that Krill oil lowers serum TG levels in subjects with borderline high or high fasting TG levels. To test our hypothesis 300 male and female subjects were included in a double-blind, randomized, multi-center, placebo-controlled study with five treatment groups: placebo (olive oil) or 0.5, 1, 2, or 4 g/day of krill oil. Serum lipids were measured after an overnight fast at baseline, 6 and 12 weeks. Due to a high intra-individual variability in TG levels, data from all subjects in the four krill oil groups were pooled to increase statistical power, and a general time- and dose-independent one-way analysis of variance was performed to assess efficacy. Relative to subjects in the placebo group, those administered krill oil had a statistically significant calculated reduction in serum TG levels of 10.2%. Moreover, LDL-C levels were not increased in the krill oil groups relative to the placebo group. The outcome of the pooled analysis suggests that krill oil is effective in reducing a cardiovascular risk factor. However, owing to the individual fluctuations of TG concentrations measured, a study with more individual measurements per treatment group is needed to increase the confidence of these findings.
Assuntos
LDL-Colesterol/sangue , Gorduras na Dieta/uso terapêutico , Suplementos Nutricionais , Euphausiacea , Hipertrigliceridemia/tratamento farmacológico , Óleos/uso terapêutico , Triglicerídeos/sangue , Adulto , Animais , Gorduras na Dieta/farmacologia , Método Duplo-Cego , Feminino , Humanos , Hipertrigliceridemia/prevenção & controle , Masculino , Pessoa de Meia-Idade , Óleos/farmacologiaRESUMO
The safety of krill oil was assessed in a subchronic toxicity study and in a genotoxicity test. In a 13-week study, rats were fed krill oil or control diets. There were no differences noted in body weight, food consumption or in the functional observation battery parameters in either gender. Differences in both haematology and clinical chemistry values were noted in the krill oil-treated groups. However these findings were of no toxicological significance. Significant decreases in absolute and covariant heart weight in some krill oil-treated animals were noted although no corresponding histological changes were observed. In addition, periportal microvesicular hepatocyte vacuolation was noted histologically in males fed 5% krill oil. This finding was not associated with other indications of hepatic dysfunction. Given that the effects of the 13-week toxicity study were non-toxic in nature, the no observed adverse effect level (NOAEL) for the conditions of this study was considered to be 5% krill oil. The genotoxicity experiments documented no mutagenicity of krill oil in bacteria.
RESUMO
BACKGROUND: The purpose of the study was to evaluate the effects of krill oil (KO) on cognition and depression-like behaviour in rats. METHODS: Cognition was assessed using the Aversive Light Stimulus Avoidance Test (ALSAT). The Unavoidable Aversive Light Stimulus (UALST) and the Forced Swimming Test (FST) were used to evaluate the antidepressant-like effects of KO. Imipramine (IMIP) was used as the antidepressant reference substance. RESULTS: After 7 weeks of KO intake, both males and females treated with KO were significantly better in discriminating between the active and the inactive levers in the ALSAT from day 1 of training (p<0.01). Both KO and IMIP prevented resignation/depression on the third day in the UALST. Similarly, a shorter immobility time was observed for the KO and IMIP groups compared to the control in the FST (p<0.001). These data support a robust antidepressant-like potential and beneficial cognitive effect of KO. Changes in expression of synaptic plasticity-related genes in the prefrontal cortex and hippocampus were also investigated. mRNA for brain-derived neurotrophic factor (Bdnf) was specifically upregulated in the hippocampus of female rats receiving 7 weeks of KO supplementation (p=0.04) and a similar trend was observed in males (p=0.08). Males also exhibited an increase in prefrontal cortex expression of Arc mRNA, a key protein in long-term synaptic plasticity (p=0.05). IMIP induced clear effects on several plasticity related genes including Bdnf and Arc. CONCLUSIONS: These results indicate that active components (eicosapentaenoic acid, docosahexaenoic acid and astaxanthin) in KO facilitate learning processes and provide antidepressant-like effects. Our findings also suggest that KO might work through different physiological mechanisms than IMIP.
Assuntos
Antidepressivos/farmacologia , Cognição/efeitos dos fármacos , Depressão/prevenção & controle , Gorduras Insaturadas na Dieta/farmacologia , Euphausiacea/química , Nootrópicos/farmacologia , Animais , Antidepressivos/isolamento & purificação , Aprendizagem da Esquiva/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Depressão/metabolismo , Depressão/fisiopatologia , Gorduras Insaturadas na Dieta/isolamento & purificação , Feminino , Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Imipramina/farmacologia , Masculino , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Plasticidade Neuronal/efeitos dos fármacos , Nootrópicos/isolamento & purificação , Córtex Pré-Frontal/efeitos dos fármacos , Ratos , Ratos Wistar , NataçãoRESUMO
BACKGROUND: Excess peroxisome proliferator-activated receptor (PPAR) stimulation has been associated with detrimental health effects including impaired myocardial function. Recently, supplementation with n-3 polyunsaturated fatty acids (PUFA) has been associated with improved left ventricular function and functional capacity in patients with dilated cardiomyopathy. We investigated the long-term effects of the pan-PPAR agonist tetradecylthioacetic acid (TTA) and/or high-dose fish oil (FO) on cardiac fatty acid (FA) composition and lipid metabolism. Male Wistar rats were given one out of four different 25% (w/v) fat diets: control diet; TTA diet; FO diet; or diet containing both TTA and FO. RESULTS: After 50 weeks n-3 PUFA levels were increased by TTA and FO in the heart, whereas liver levels were reduced following TTA administration. TTA was associated with a decrease in arachidonic acid, increased activities of carnitine palmitoyltransferase II, fatty acyl-CoA oxidase, glycerol-3-phosphate acyltransferase, and fatty acid synthase in the heart. Furthermore, cardiac Ucp3 and Cact mRNA was upregulated. CONCLUSIONS: Long-term treatment with the pan-PPAR agonist TTA or high-dose FO induced marked changes in PUFA composition and enzymatic activity involved in FA metabolism in the heart, different from liver. Changes included increased FA oxidation and a selective increase in cardiac n-3 PUFA.
Assuntos
Ácidos Graxos Ômega-3/metabolismo , Óleos de Peixe/administração & dosagem , Miocárdio/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/agonistas , Sulfetos/administração & dosagem , Acil-CoA Oxidase/metabolismo , Animais , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Óleos de Peixe/farmacologia , Expressão Gênica , Glicerol-3-Fosfato O-Aciltransferase/metabolismo , Canais Iônicos/genética , Canais Iônicos/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Miocárdio/enzimologia , Especificidade de Órgãos , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Ratos , Ratos Wistar , Sulfetos/farmacologia , Fatores de Tempo , Proteína Desacopladora 3RESUMO
Krill oil (KO) is a dietary source of n-3 polyunsaturated fatty acids, mainly represented by eicosapentaenoic acid and docosahexaenoic acid bound to phospholipids. The supplementation of a high-fat diet with 2.5% KO efficiently prevented triglyceride and cholesterol accumulation in liver of treated rats. This effect was accompanied by a parallel reduction of the plasma levels of triglycerides and glucose and by the prevention of a plasma insulin increase. The investigation of the molecular mechanisms of KO action in high-fat fed animals revealed a strong decrease in the activities of the mitochondrial citrate carrier and of the cytosolic acetyl-CoA carboxylase and fatty acid synthetase, which are both involved in hepatic de novo lipogenesis. In these animals a significant increase in the activity of carnitine palmitoyl-transferase I and in the levels of carnitine was also observed, suggesting a concomitant stimulation of hepatic fatty acid oxidation. The KO supplemented animals also retained an efficient mitochondrial oxidative phosphorylation, most probably as a consequence of a KO-induced arrest of the uncoupling effects of a high-fat diet. Lastly, the KO supplementation prevented an increase in body weight, as well as oxidative damage of lipids and proteins, which is often found in high-fat fed animals.
Assuntos
Suplementos Nutricionais , Euphausiacea/química , Fígado Gorduroso/prevenção & controle , Óleos/farmacologia , Acetil-CoA Carboxilase/metabolismo , Animais , Western Blotting , Peso Corporal/efeitos dos fármacos , Carnitina O-Palmitoiltransferase/metabolismo , Proteínas de Transporte/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ingestão de Alimentos/efeitos dos fármacos , Ácido Graxo Sintases/metabolismo , Ácidos Graxos/biossíntese , Ácidos Graxos Ômega-3/biossíntese , Ácidos Graxos Ômega-3/química , Ácidos Graxos Ômega-3/farmacologia , Fígado Gorduroso/sangue , Fígado Gorduroso/etiologia , Lipídeos/análise , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Óleos/química , Tamanho do Órgão/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Fosforilação Oxidativa/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
The 3-thia fatty acid tetradecylthioacetic acid (TTA) is a synthetic modified fatty acid, which, similar with dietary fish oil (FO), influences the regulation of lipid metabolism, the inflammatory response and redox status. This study was aimed to penetrate the difference in TTA's mode of action compared to FO in a long-term experiment (50 weeks of feeding). Male Wistar rats were fed a control, high-fat (25% w/v) diet or a high-fat diet supplemented with either TTA (0.375% w/v) or FO (10% w/v) or their combination. Plasma fatty acid composition, hepatic lipids and expression of relevant genes in the liver and biomarkers of oxidative damage to protein were assessed at the end point of the experiment. Both supplements given in combination demonstrated an additive effect on the decrease in plasma cholesterol levels. The FO diet alone led to removal of plasma cholesterol and a concurrent cholesterol accumulation in liver; however, with TTA cotreatment, the hepatic cholesterol level was significantly reduced. Dietary FO supplementation led to an increased oxidative damage, as seen by biomarkers of protein oxidation and lipoxidation. Tetradecylthioacetic acid administration reduced the levels of these biomarkers confirming its protective role against lipoxidation and protein oxidative damage. Our findings explore the lipid reducing effects of TTA and FO and demonstrate that these bioactive dietary compounds might act in a different manner. The experiment confirms the antioxidant capacity of TTA, showing an improvement in FO-induced oxidative stress.
Assuntos
Antioxidantes/farmacologia , Óleos de Peixe/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Sulfetos/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Dieta Hiperlipídica , Suplementos Nutricionais , Enzimas/genética , Enzimas/metabolismo , Ácidos Graxos/análise , Ácidos Graxos/sangue , Ácidos Graxos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Canais Iônicos/genética , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Proteínas Mitocondriais/genética , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Proteína Desacopladora 2 , Proteína Desacopladora 3RESUMO
BACKGROUND: In the western world, heart failure (HF) is one of the most important causes of cardiovascular mortality. Supplement with n-3 polyunsaturated fatty acids (PUFA) has been shown to improve cardiac function in HF and to decrease mortality after myocardial infarction (MI). The molecular structure and composition of n-3 PUFA varies between different marine sources and this may be of importance for their biological effects. Krill oil, unlike fish oil supplements, contains the major part of the n-3 PUFA in the form of phospholipids. This study investigated effects of krill oil on cardiac remodeling after experimental MI. Rats were randomised to pre-treatment with krill oil or control feed 14 days before induction of MI. Seven days post-MI, the rats were examined with echocardiography and rats in the control group were further randomised to continued control feed or krill oil feed for 7 weeks before re-examination with echocardiography and euthanization. RESULTS: The echocardiographic evaluation showed significant attenuation of LV dilatation in the group pretreated with krill oil compared to controls. Attenuated heart weight, lung weight, and levels of mRNA encoding classical markers of LV stress, matrix remodeling and inflammation reflected these findings. The total composition of fatty acids were examined in the left ventricular (LV) tissue and all rats treated with krill oil showed a significantly higher proportion of n-3 PUFA in the LV tissue, although no difference was seen between the two krill oil groups. CONCLUSIONS: Supplement with krill oil leads to a proportional increase of n-3 PUFA in myocardial tissue and supplement given before induction of MI attenuates LV remodeling.
Assuntos
Cardiotônicos/farmacologia , Dilatação Patológica/prevenção & controle , Euphausiacea/química , Ácidos Graxos Ômega-3/farmacologia , Infarto do Miocárdio/patologia , Óleos/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Cardiotônicos/uso terapêutico , Ácidos Graxos Ômega-3/uso terapêutico , Expressão Gênica/efeitos dos fármacos , Coração/efeitos dos fármacos , Coração/fisiopatologia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Lipídeos/sangue , Masculino , Miocárdio/enzimologia , Miocárdio/metabolismo , Miocárdio/patologia , Óleos/uso terapêutico , Tamanho do Órgão/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
BACKGROUND: Previous reports have shown an antiproliferative effect of the synthetic, 3-thia fatty acid tetradecylthioacetic acid (TTA) on different cancer cells in vitro and in vivo. The mechanisms behind the observed effects are poorly understood. We therefore wanted to explore the molecular mechanisms involved in TTA-induced growth inhibition of the human colon cancer cell line SW620 by gene expression profiling. METHODS: An antiproliferative effect of TTA on SW620 cells in vitro was displayed in real time using the xCELLigence System (Roche). Affymetrix gene expression profiling was performed to elucidate the molecular mechanisms behind the antiproliferative effect of TTA. Changes in gene expression were verified at protein level by western blotting. RESULTS: TTA reduced SW620 cell growth, measured as baseline cell index, by 35% and 55% after 48 h and 72 h, respectively. We show for the first time that TTA induces an endoplasmic reticulum (ER) stress response in cancer cells. Gene expression analysis revealed changes related to ER stress and unfolded protein response (UPR). This was verified at protein level by phosphorylation of eukaryote translation initiation factor 2 alpha (eIF2α) and downstream up-regulation of activating transcription factor 4 (ATF4). Transcripts for positive and negative cell cycle regulators were down- and up-regulated, respectively. This, together with a down-regulation of Cyclin D1 at protein level, indicates inhibition of cell cycle progression. TTA also affected transcripts involved in calcium homeostasis. Moreover, mRNA and protein level of the ER stress inducible C/EBP-homologous protein (CHOP), Tribbles homolog 3 (Drosophila) (TRIB3) and CCAAT/enhancer binding protein beta (C/EBPß) were enhanced, and the C/EBPß LIP/LAP ratio was significantly increased. These results indicate prolonged ER stress and a possible link to induction of cell death. CONCLUSION: We find that TTA-induced growth inhibition of SW620 cells seems to be mediated through induction of ER stress and activation of the UPR pathway.
Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Sulfetos/farmacologia , Fator 6 Ativador da Transcrição/genética , Fator 6 Ativador da Transcrição/metabolismo , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo , Endorribonucleases/genética , Endorribonucleases/metabolismo , Fator de Iniciação 2 em Eucariotos/genética , Fator de Iniciação 2 em Eucariotos/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , ATPases Transportadoras de Cálcio da Membrana Plasmática/genética , ATPases Transportadoras de Cálcio da Membrana Plasmática/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transcrição Gênica , Resposta a Proteínas não Dobradas/efeitos dos fármacosRESUMO
BACKGROUND: Omega-3 polyunsaturated fatty acids (ω-3-PUFA) are known to ameliorate several metabolic risk factors for cardiovascular disease, and an association between elevated peripheral levels of endogenous ligands of cannabinoid receptors (endocannabinoids) and the metabolic syndrome has been reported. We investigated the dose-dependent effects of dietary ω-3-PUFA supplementation, given as krill oil (KO), on metabolic parameters in high fat diet (HFD)-fed mice and, in parallel, on the levels, in inguinal and epididymal adipose tissue (AT), liver, gastrocnemius muscle, kidneys and heart, of: 1) the endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG), 2) two anandamide congeners which activate PPARα but not cannabinoid receptors, N-oleoylethanolamine and N-palmitoylethanolamine, and 3) the direct biosynthetic precursors of these compounds. METHODS: Lipids were identified and quantified using liquid chromatography coupled to atmospheric pressure chemical ionization single quadrupole mass spectrometry (LC-APCI-MS) or high resolution ion trap-time of flight mass spectrometry (LC-IT-ToF-MS). RESULTS: Eight-week HFD increased endocannabinoid levels in all tissues except the liver and epididymal AT, and KO reduced anandamide and/or 2-AG levels in all tissues but not in the liver, usually in a dose-dependent manner. Levels of endocannabinoid precursors were also generally down-regulated, indicating that KO affects levels of endocannabinoids in part by reducing the availability of their biosynthetic precursors. Usually smaller effects were found of KO on OEA and PEA levels. CONCLUSIONS: Our data suggest that KO may promote therapeutic benefit by reducing endocannabinoid precursor availability and hence endocannabinoid biosynthesis.
RESUMO
The administration of tetradecylthioacetic acid (TTA), a hypolipidemic and anti-inflammatory modified bioactive fatty acid, has in several experiments based on high fat diets been shown to improve lipid transport and utilization. It was suggested that increased mitochondrial and peroxisomal fatty acid oxidation in the liver of Wistar rats results in reduced plasma triacylglycerol (TAG) levels. Here we assessed the potential of TTA to prevent tumor necrosis factor (TNF) α-induced lipid modifications in human TNFα (hTNFα) transgenic mice. These mice are characterized by reduced ß-oxidation and changed fatty acid composition in the liver. The effect of dietary treatment with TTA on persistent, low-grade hTNFα overexpression in mice showed a beneficial effect through decreasing TAG plasma concentrations and positively affecting saturated and monounsaturated fatty acid proportions in the liver, leading to an increased anti-inflammatory fatty acid index in this group. We also observed an increase of mitochondrial ß-oxidation in the livers of TTA treated mice. Concomitantly, there were enhanced plasma levels of carnitine, acetyl carnitine, propionyl carnitine, and octanoyl carnitine, no changed levels in trimethyllysine and palmitoyl carnitine, and a decreased level of the precursor for carnitine, called γ-butyrobetaine. Nevertheless, TTA administration led to increased hepatic TAG levels that warrant further investigations to ascertain that TTA may be a promising candidate for use in the amelioration of inflammatory disorders characterized by changed lipid metabolism due to raised TNFα levels.
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Antioxidantes/metabolismo , Ácidos Graxos/metabolismo , Inflamação/metabolismo , Mitocôndrias Hepáticas/metabolismo , Oxirredução , Sulfetos/metabolismo , Animais , Antioxidantes/administração & dosagem , Doença Crônica , Dieta , Ácidos Graxos/química , Feminino , Humanos , Lipídeos/sangue , Lipídeos/química , Camundongos , Camundongos Transgênicos , Ratos , Sulfetos/administração & dosagem , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
We have previously shown that krill oil (KO), more efficiently than fish oil, was able to downregulate the endocannabinoid system in different tissues of obese zucker rats.We therefore aimed at investigating whether an intake of 2 g/d of either KO or menhaden oil (MO), which provides 309 mg/d of EPA/DHA 2:1 and 390 mg/d of EPA/DHA 1:1 respectively, or olive oil (OO) for four weeks, is able to modify plasma endocannabinoids in overweight and obese subjects.The results confirmed data in the literature describing increased levels of endocannabinoids in overweight and obese with respect to normo-weight subjects. KO, but not MO or OO, was able to significantly decrease 2-arachidonoylglycerol (2-AG), although only in obese subjects. In addition, the decrease of 2-AG was correlated to the plasma n-6/n-3 phospholipid long chain polyunsaturated fatty acid (LCPUFA) ratio. These data show for the first time in humans that relatively low doses of LCPUFA n-3 as KO can significantly decrease plasma 2-AG levels in obese subjects in relation to decrease of plasma phospholipid n-6/n-3 LCPUFA ratio. This effect is not linked to changes of metabolic syndrome parameters but is most likely due to a decrease of 2-AG biosynthesis caused by the replacement of 2-AG ultimate precursor, arachidonic acid, with n-3 PUFAs, as previously described in obese Zucker rats.
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High performance liquid chromatography-electrospray tandem mass spectrometry was used to elucidate the phospholipids in krill oil extracted from Euphausia superba, an emerging source for human nutritional supplements. The study was carried out in order to map the species of the choline-containing phospholipid classes: phosphatidylcholine and lyso-phosphatidylcholine. In addition, the prevalent phosphatidylcholine class was quantified and the results compared with prior analysis. The qualification was performed with separation on a reverse phase chromatography column, while the quantification was obtained with class separation on a normal phase chromatography column. An Orbitrap system was used for the detection, and pulsed-Q dissociation fragmentation was utilized for the identification of the species. An asymmetrical exclusion list was applied for detection of phospholipid species of lower concentration, significantly improving the number of species observed. A total of 69 choline-containing phospholipids were detected, whereof 60 phosphatidylcholine substances, among others seven with probable omega-3 fatty acids in both sn-1 and sn-2. The phosphatidylcholine concentration was estimated to be 34 ± 5 g/100 g oil (n = 5). These results confirm the complexity of the phospholipid composition of krill oil, and the presence of long chained, heavily unsaturated fatty acids.
Assuntos
Euphausiacea/química , Euphausiacea/metabolismo , Fosfatidilcolinas/química , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Ácidos Graxos Ômega-3/química , Óleos/química , Fosfatidilcolinas/análise , Espectrometria de Massas em TandemRESUMO
The purpose of the present study is to investigate the effects of krill oil and fish oil on serum lipids and markers of oxidative stress and inflammation and to evaluate if different molecular forms, triacylglycerol and phospholipids, of omega-3 polyunsaturated fatty acids (PUFAs) influence the plasma level of EPA and DHA differently. One hundred thirteen subjects with normal or slightly elevated total blood cholesterol and/or triglyceride levels were randomized into three groups and given either six capsules of krill oil (N = 36; 3.0 g/day, EPA + DHA = 543 mg) or three capsules of fish oil (N = 40; 1.8 g/day, EPA + DHA = 864 mg) daily for 7 weeks. A third group did not receive any supplementation and served as controls (N = 37). A significant increase in plasma EPA, DHA, and DPA was observed in the subjects supplemented with n-3 PUFAs as compared with the controls, but there were no significant differences in the changes in any of the n-3 PUFAs between the fish oil and the krill oil groups. No statistically significant differences in changes in any of the serum lipids or the markers of oxidative stress and inflammation between the study groups were observed. Krill oil and fish oil thus represent comparable dietary sources of n-3 PUFAs, even if the EPA + DHA dose in the krill oil was 62.8% of that in the fish oil.
Assuntos
Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Óleos de Peixe/farmacologia , Animais , Colesterol/sangue , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/sangue , Euphausiacea , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Óleos de Peixe/administração & dosagem , Humanos , Masculino , Óleos/química , Óleos/farmacologia , Triglicerídeos/sangueRESUMO
Dietary supplementation with ω-3 polyunsaturated fatty acids (ω-3 PUFAs), specifically the fatty acids docosahexaenoic acid (DHA; 22:6 ω-3) and eicosapentaenoic acid (EPA; 20:5 ω-3), is known to have beneficial health effects including improvements in glucose and lipid homeostasis and modulation of inflammation. To evaluate the efficacy of two different sources of ω-3 PUFAs, we performed gene expression profiling in the liver of mice fed diets supplemented with either fish oil (FO) or krill oil (KO). We found that ω-3 PUFA supplements derived from a phospholipid krill fraction (KO) downregulated the activity of pathways involved in hepatic glucose production as well as lipid and cholesterol synthesis. The data also suggested that KO-supplementation increases the activity of the mitochondrial respiratory chain. Surprisingly, an equimolar dose of EPA and DHA derived from FO modulated fewer pathways than a KO-supplemented diet and did not modulate key metabolic pathways regulated by KO, including glucose metabolism, lipid metabolism and the mitochondrial respiratory chain. Moreover, FO upregulated the cholesterol synthesis pathway, which was the opposite effect of krill-supplementation. Neither diet elicited changes in plasma levels of lipids, glucose, or insulin, probably because the mice used in this study were young and were fed a low-fat diet. Further studies of KO-supplementation using animal models of metabolic disorders and/or diets with a higher level of fat may be required to observe these effects.
RESUMO
BACKGROUND: Although the efficacy of standard fish oil has been the subject of research in arthritis, the effect of krill oil in this disease has yet to be investigated. The objective of the present study was to evaluate a standardised preparation of krill oil and fish oil in an animal model for arthritis. METHODS: Collagen-induced arthritis susceptible DBA/1 mice were provided ad libitum access to a control diet or diets supplemented with either krill oil or fish oil throughout the study. There were 14 mice in each of the 3 treatment groups. The level of EPA + DHA was 0.44 g/100 g in the krill oil diet and 0.47 g/100 g in the fish oil diet. Severity of arthritis was determined using a clinical scoring system. Arthritis joints were analysed by histopathology and graded. Serum samples were obtained at the end of the study and the levels of IL-1alpha, IL-1beta, IL-7, IL-10, IL-12p70, IL-13, IL-15, IL-17 and TGF-beta were determined by a Luminex assay system. RESULTS: Consumption of krill oil and supplemented diet significantly reduced the arthritis scores and hind paw swelling when compared to a control diet not supplemented with EPA and DHA. However, the arthritis score during the late phase of the study was only significantly reduced after krill oil administration. Furthermore, mice fed the krill oil diet demonstrated lower infiltration of inflammatory cells into the joint and synovial layer hyperplasia, when compared to control. Inclusion of fish oil and krill oil in the diets led to a significant reduction in hyperplasia and total histology score. Krill oil did not modulate the levels of serum cytokines whereas consumption of fish oil increased the levels of IL-1alpha and IL-13. CONCLUSIONS: The study suggests that krill oil may be a useful intervention strategy against the clinical and histopathological signs of inflammatory arthritis.
Assuntos
Artrite Experimental/tratamento farmacológico , Artrite Experimental/prevenção & controle , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/prevenção & controle , Suplementos Nutricionais , Euphausiacea/química , Ácidos Graxos Ômega-3/farmacologia , Animais , Colágeno/farmacologia , Citocinas/sangue , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/uso terapêutico , Euphausiacea/fisiologia , Ácidos Graxos Ômega-3/uso terapêutico , Óleos de Peixe/farmacologia , Óleos de Peixe/uso terapêutico , Mediadores da Inflamação/sangue , Interleucinas/sangue , Masculino , Camundongos , Camundongos Endogâmicos DBA , Ratos , Ratos Wistar , Frutos do Mar , Resultado do TratamentoRESUMO
Antarctic krill, also known as Euphausia superba, is a marine crustacean rich in both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We tested the hypothesis that krill oil would increase plasma concentrations of EPA and DHA without adversely affecting indicators of safety, tolerability, or selected metabolic parameters. In this randomized, double-blind parallel arm trial, overweight and obese men and women (N = 76) were randomly assigned to receive double-blind capsules containing 2 g/d of krill oil, menhaden oil, or control (olive) oil for 4 weeks. Results showed that plasma EPA and DHA concentrations increased significantly more (P < .001) in the krill oil (178.4 +/- 38.7 and 90.2 +/- 40.3 micromol/L, respectively) and menhaden oil (131.8 +/- 28.0 and 149.9 +/- 30.4 micromol/L, respectively) groups than in the control group (2.9 +/- 13.8 and -1.1 +/- 32.4 micromol/L, respectively). Systolic blood pressure declined significantly more (P < .05) in the menhaden oil (-2.2 +/- 2.0 mm Hg) group than in the control group (3.3 +/- 1.5 mm Hg), and the response in the krill oil group (-0.8 +/- 1.4 mm Hg) did not differ from the other 2 treatments. Blood urea nitrogen declined in the krill oil group as compared with the menhaden oil group (P < .006). No significant differences for other safety variables were noted, including adverse events. In conclusion, 4 weeks of krill oil supplementation increased plasma EPA and DHA and was well tolerated, with no indication of adverse effects on safety parameters.
Assuntos
Gorduras na Dieta/farmacologia , Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/sangue , Euphausiacea/química , Sobrepeso/dietoterapia , Animais , Pressão Sanguínea/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Gorduras na Dieta/administração & dosagem , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/farmacologia , Método Duplo-Cego , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/farmacologia , Feminino , Óleos de Peixe/administração & dosagem , Óleos de Peixe/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/dietoterapia , Azeite de Oliva , Sobrepeso/sangue , Óleos de Plantas/administração & dosagem , Óleos de Plantas/farmacologiaRESUMO
Krill oil (KO) is rich in n-3 fatty acids that are present in phospholipids rather than in triglycerides. In the present study, we investigated the effects of dietary KO on cardiometabolic risk factors in male C57BL/6 mice fed a high-fat diet. Mice (n = 6-10 per group) were fed for 8 weeks either: (1) a nonpurified chow diet (N); (2) a high-fat semipurified diet containing 21 wt % buttermilk + 0.15 wt % cholesterol (HF); (3) HF supplemented with 1.25 wt % KO (HFKO1.25); (4) HF with 2.5 wt % KO (HFKO2.5); or (5) HF with 5 wt % KO (HFKO5.0). Dietary KO supplementation caused a significant reduction in liver wt (i.e., hepatomegaly) and total liver fat (i.e., hepatic steatosis), due to a dose-dependent reduction in hepatic triglyceride (mean +/- SEM: 35 +/- 6, 47 +/- 4, and 51 +/- 5% for HFKO1.25, -2.5, and -5.0 vs HF, respectively, P < 0.001) and cholesterol (55 +/- 5, 66 +/- 3, and 71 +/- 3%, P < 0.001). Serum cholesterol levels were reduced by 20 +/- 3, 29 +/- 4, and 29 +/- 5%, and blood glucose was reduced by 36 +/- 5, 34 +/- 6, and 42 +/- 6%, respectively. Serum adiponectin was increased in KO-fed animals (HF vs HFKO5.0: 5.0 +/- 0.2 vs 7.5 +/- 0.6 microg/mL, P < 0.01). These results demonstrate that dietary KO is effective in improving metabolic parameters in mice fed a high-fat diet, suggesting that KO may be of therapeutic value in patients with the metabolic syndrome and/or nonalcoholic fatty liver disease.
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Glicemia/análise , Gorduras Insaturadas na Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Euphausiacea/química , Fígado Gorduroso/prevenção & controle , Hipercolesterolemia/prevenção & controle , Adiponectina/sangue , Animais , Colesterol/sangue , Ácidos Graxos Ômega-3/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Tetradecylthioacetic acid (TTA) is a hypolipidemic modified fatty acid and a peroxisome proliferator-activated receptor (PPAR) ligand. The mechanisms of TTA-mediated effects seem to involve the PPARs, but the effects have not been assigned to any specific PPAR subtype. PPARalpha-/- mice were employed to study the role of PPARalpha after TTA treatment. We also performed in vitro transfection assays to obtain mechanistic knowledge of how TTA affected PPAR activation in the presence of PPARgamma coactivator (PGC)-1 and steroid receptor coactivators (SRC)-1 and SRC-2, which are associated with energy balance and mitochondrial biogenesis. We show that TTA increases hepatic fatty acid beta-oxidation in PPARalpha-/- mice. TTA acts as a pan-PPAR ligand in vitro, and PGC-1, SRC-1 and SRC-2 have cell type and PPAR-specific effects together with TTA. In the absence of exogenous ligands, SRC-1 did not induce PPAR activity, while PGC-1 was the most potent PPAR coactivator. When the coactivators were overexpressed, pronounced effects of TTA were observed especially for PPARdelta and PPARgamma. We conclude that PPARalpha is involved in, but not required for, the hypolipidemic mechanisms of TTA. It appears that the activity of PPARdelta, with substantial contribution of nuclear receptor coactivators, PGC-1 in special, is conducive to TTA's mechanism of action.
Assuntos
Ácidos Graxos/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , PPAR alfa/deficiência , PPAR delta/metabolismo , Sulfetos/farmacologia , Transativadores/metabolismo , Animais , Linhagem Celular Tumoral , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Humanos , Ligantes , Camundongos , Coativador 1 de Receptor Nuclear , Coativador 2 de Receptor Nuclear/genética , Coativador 2 de Receptor Nuclear/metabolismo , Oxirredução/efeitos dos fármacos , PPAR alfa/agonistas , PPAR alfa/genética , PPAR alfa/metabolismo , PPAR delta/genética , PPAR gama/genética , PPAR gama/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Transativadores/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ativação Transcricional/efeitos dos fármacosRESUMO
PURPOSE: To evaluate the effects of diets supplemented with the modified fatty acid tetradecylthioacetic acid (TTA) and fish protein hydrolysate (FPH) on tumor growth of the human colon cancer cell line SW620, and to investigate the properties of tumor vasculature by dynamic contrast-enhanced MRI in a human tumor xenograft. EXPERIMENTAL DESIGN: SW620 cells were grown in vitro in presence of TTA and palmitic acid and proliferation was measured by thymidine incorporation. The xenograft study in mice was performed with four distinct diets: (a) control diet; (b) diet with TTA; (c) diet with TTA and FPH; and (d) diet with FPH. SW620 cells were injected subcutaneously, and dynamic contrast enhanced (DCE) MRI was performed on a Bruker BioSpec 7T system. The data was analyzed by two-compartment modeling of the contrast enhancement, initial area under the curve (IAUC) and by use of relative signal intensity (RSI) distributions. RESULTS: The in vitro cell studies revealed that TTA reduced tumor cell proliferation as a function of both dose and time. The in vivo tumor growth was significantly reduced for the two groups fed TTA, as compared to the control group. The mean 10(th) percentile RSI, v(e) and IAUC for the TTA group were significant higher than for the control group. CONCLUSIONS: This study confirms the growth inhibitory effects of TTA, both in vitro and in vivo, in a colon cancer model. The analysis of DCE-MRI data showed that TTA influences the vascular properties of the tumor in addition to the growth.