RESUMO
Maternal docosahexaenoic acid (DHA) is required during pregnancy to supply for normal fetal growth and development. This pilot study aimed to assess the unknown fatty acid (FA) composition in a cohort of non-pregnant and pregnant Israeli women at term and their offspring on a normal diet without n-3 FA supplementation. The fatty acid profile, analyzed using gas chromatography, showed significantly higher plasma monounsaturated (MUFA) and lower n-6 FA percent distribution with similar n-3 index, in pregnant compared to non-pregnant women. RBC exhibited significantly higher MUFA with similar n-3 index, in pregnant compared to non-pregnant women. N-3 FA significantly correlated between neonates' plasma, with higher n-3 index, and pregnant women's DHA. Conclusion: DHA levels in non-pregnant and pregnant Israeli women at term were comparable and the DHA in pregnant women's plasma positively correlated with their neonate's level, suggesting an efficient mother-fetus FA transfer and/or fetal fatty acid metabolism to longer FA products.
Assuntos
Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Troca Materno-Fetal , Adulto , Proteínas de Arabidopsis/sangue , Carbono-Oxigênio Ligases/sangue , Estudos de Casos e Controles , Ácidos Docosa-Hexaenoicos/sangue , Ácidos Graxos Essenciais/sangue , Ácidos Graxos Insaturados/sangue , Feminino , Humanos , Recém-Nascido , Israel , Fenômenos Fisiológicos da Nutrição Materna , Projetos Piloto , Gravidez , Triglicerídeos/sangue , Ácido alfa-Linolênico/sangue , Ácido gama-Linolênico/sangueRESUMO
Docosahexaenoic acid (DHA) is critical for normal brain development and function. DHA is in danger of being significantly reduced in the human food supply, and the question of whether its metabolic precursor, the essential n-3 alpha linolenic acid (ALA) during pregnancy, can support fetal brain DHA levels for optimal neurodevelopment, is fundamental. Female mice were fed either ALA-enriched or Control diet during pregnancy and lactation. The direct effect of maternal dietary ALA on lipids was analyzed in liver, red blood cells, brain and brain vasculature, together with genes of fatty acid metabolism and transport in three-week-old offspring. The long-term effect of maternal dietary ALA on brain fatty acids and memory was studied in 19-week-old offspring. Three-week-old ALA offspring showed higher levels of n-3 fatty acids in liver, red blood cell, blood-brain barrier (BBB) vasculature and brain parenchyma, DHA enrichment in brain phospholipids and higher gene and protein expression of the DHA transporter, major facilitator superfamily domain containing 2a, compared to Controls. 19-week-old ALA offspring showed higher brain DHA levels and better memory performance than Controls. The increased brain DHA levels induced by maternal dietary ALA during pregnancy-lactation, together with the up-regulated levels of major facilitator superfamily domain containing 2a, may indicate a mode for greater DHA uptake with long-term impact on better memory in ALA offspring.
Assuntos
Encéfalo/metabolismo , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido alfa-Linolênico/farmacologia , Animais , Animais Recém-Nascidos , Encéfalo/efeitos dos fármacos , Feminino , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , DesmameRESUMO
SCOPE: In females, hyperglycemia abolishes estrogen-vascular protection, leading to inflammation and oxidative stress that are related to diabetes-associated cardiovascular complications. Such knowledge led us to examine the potential of glabridin, as a replacement of estrogen anti-inflammatory activity under high-glucose conditions. METHODS AND RESULTS: In macrophage-like cells, chronic glucose stress (28 and 44 mM) upregulated inducible nitric oxide synthase (iNOS) mRNA expression by 42 and 189%, respectively. Pretreatment with glabridin, under chronic glucose stress, downregulated the LPS-induced nitric oxide secretion and nitrotyrosine formation, by 39 and 21%, respectively. Pretreatment with estradiol did not prevent the LPS-induced nitrotyrosine formation. Furthermore, glabridin, brought about a decrease in the LPS-induced iNOS mRNA expression by 48%, as compared to cells pretreated with estradiol. Glabridin decreased protein levels of liver iNOS by 69% in adult mouse offspring which developed hyperglycemia after early fetal exposure to a saturated fatty acid-enriched maternal diet. Glabridin also decreased liver nitrotyrosine levels in offspring of regular diet-fed mothers after further receiving high-fat diet. CONCLUSION: Such results indicate that glabridin retains anti-inflammatory abilities to regulate the synthesis and activity of iNOS under high-glucose levels, implying that a glabridin supplement may serve as an anti-inflammatory agent in diabetes-related vascular dysfunction.
Assuntos
Glycyrrhiza/química , Inflamação/tratamento farmacológico , Isoflavonas/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo , Fenóis/farmacologia , Raízes de Plantas/química , Animais , Anti-Inflamatórios/farmacologia , Glicemia/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Hiperglicemia/tratamento farmacológico , Inflamação/induzido quimicamente , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/efeitos adversos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Estresse Fisiológico , Fator de Necrose Tumoral alfa/metabolismo , Tirosina/análogos & derivados , Tirosina/antagonistas & inibidores , Tirosina/metabolismo , Regulação para CimaRESUMO
Long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) exert health benefits which are dependent upon their incorporation into blood, cells and tissues. Plasma and tissue deposition of LC n-3 PUFA from oils extracted from the micro-algae Nannochloropsis oculata and from krill were compared in rats. The algal oil provides eicosapentaenoic acid (EPA) partly conjugated (15%) to phospholipids and glycolipids but no docosahexaenoic acid (DHA), whereas krill oil provides both EPA and DHA conjugated in part (40%) to phospholipids. Rats fed a standard diet received either krill oil or polar-lipid rich algal oil by gavage daily for 7 days (5 ml oil per kg body weight each day). Fatty acid concentrations were analyzed in plasma, brain and liver, and two adipose depots since these represent transport, functional and storage pools of fatty acids, respectively. When measuring total LC n-3 PUFA (sum of EPA, docosapentaenoic acid (DPA) and DHA), there was no statistically significant difference between the algal oil and krill oil for plasma, brain, liver and gonadal adipose tissue. Concentrations of LC n-3 PUFA were higher in the retroperitoneal adipose tissue from the algal oil group. Tissue uptake of LC n-3 PUFA from an algal oil containing 15% polar lipids (glycolipids and phospholipids) was found to be equivalent to krill oil containing 40% phospholipids. This may be due to glycolipids forming smaller micelles during ingestive hydrolysis than phospholipids. Ingestion of fatty acids with glycolipids may improve bioavailability, but this needs to be further explored.
Assuntos
Suplementos Nutricionais , Euphausiacea/química , Ácidos Graxos Ômega-3/metabolismo , Microalgas/química , Óleos/metabolismo , Estramenópilas/química , Tecido Adiposo Branco/metabolismo , Animais , Encéfalo/metabolismo , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/sangue , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/sangue , Ácido Eicosapentaenoico/metabolismo , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/sangue , Feminino , Glicolipídeos/administração & dosagem , Glicolipídeos/metabolismo , Fígado/metabolismo , Masculino , Especificidade de Órgãos , Fosfolipídeos/administração & dosagem , Fosfolipídeos/metabolismo , Ratos Sprague-DawleyRESUMO
The insulin-like growth factor (IGF) system plays a critical role in normal growth and development as well as in malignant states. Most of the biological activities of the IGFs are mediated by the IGF-IR, which is over-expressed in most tumours and cancer cell lines. Fatty acids have critical roles in both systemic physiological processes (e.g. metabolism) and cellular events (e.g. proliferation, apoptosis, signal transduction, and gene expression). Alpha-linolenic acid (ALA) and linoleic acid (LA) are essential fatty acids of the omega-3 and omega-6 families, respectively. The aim of this study was to investigate the potential interactions between fatty acids and the IGF signal transduction pathways, and to evaluate the impact of this interplay on colon cancer cells survival and proliferation. Results of Western blot analyses revealed that ALA and LA enhanced the ligand-induced IGF-IR phosphorylation and, in addition, increased receptor phosphorylation in an IGF-I independent manner. Furthermore, fatty acid treatment led to phosphorylation of downstream signalling molecules, including Akt and Erk. In addition, FACS analysis and apoptosis measurements indicated that ALA and LA have a potential mitogenic effect on HCT116 cells, as reflected by the number of cells in S phase and by a reduction of PARP cleavage, implying a reduction in apoptotic activity. In summary, our results provide evidence that omega-3 and omega-6 fatty acids modulate IGF-I action in colon cancer cells.
Assuntos
Neoplasias Colorretais/genética , Ácidos Graxos Ômega-3/genética , Ácidos Graxos Ômega-6/genética , Receptor IGF Tipo 1/metabolismo , Transdução de Sinais/fisiologia , Células HCT116 , HumanosRESUMO
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in industrialized countries. It has no accepted medical therapy. Fatty acid-bile acid conjugates (FABACs) were proven to prevent diet-induced NAFLD in rodents. AIM: This study was undertaken to test whether oral FABACs are also effective in reducing liver fat in preestablished diet-induced NAFLD. METHODS: NAFLD was induced in mice and rats by a high-fat diet and maintained by various proportions thereof. The FABACs used were conjugates of cholic acid with either arachidic or stearic acids. RESULTS: FABAC therapy reduced liver fat in all four series of experiments. The rapidity of the effect was inversely proportional to the concentration of fat in the maintenance diet. In mice on a 25% maintenance diet FABACs decreased total liver lipids by about 30% in 4 weeks (P<0.03). Diglycerides (P<0.003) and triglycerides (P<0.01) were the main neutral liver lipids that decreased during FABAC therapy. Both FABACs tested reduced liver fat in NAFLD at doses of 25 and 150 mg/kg/day. High-fat diet increased, whereas FABAC therapy decreased plasma 16 : 1/(16 : 0+16 : 1) fatty acid ratio - a marker of stearoyl CoA desaturase activity. In HepG2 cells FABACs decreased de-novo fatty acid synthesis dose dependently. CONCLUSION: Oral FABAC therapy decreased liver fat in preestablished NAFLD in mice and rats. Inhibition of stearoyl CoA desaturase activity and fatty acid synthesis are mechanisms that may contribute to this decrease. FABACs may be potential therapeutic agents for human NAFLD.
Assuntos
Ácidos e Sais Biliares/uso terapêutico , Gorduras na Dieta/efeitos adversos , Ácidos Graxos/uso terapêutico , Fígado Gorduroso/tratamento farmacológico , Animais , Glicemia/metabolismo , Ácidos Cólicos/uso terapêutico , Gorduras na Dieta/administração & dosagem , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Ácidos Graxos/biossíntese , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Metabolismo dos Lipídeos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ratos , Ratos Endogâmicos F344 , Estearoil-CoA Dessaturase/sangue , Aumento de PesoRESUMO
BACKGROUND: Fatty acid bile acid conjugates (FABACs) are novel synthetic molecules that solubilize cholesterol, prevent cholesterol crystal and gallstone formation, and dissolve pre-existing gallstones in mice. They are thus potential agents for gallstone prevention and treatment. The available knowledge concerning their biliary, systemic or possible toxic effects is, however, incomplete. AIM: To obtain information regarding biliary and systemic effects of FABACs. METHODS: Hamsters, rats and mice were administered C20-FABAC intragastrically, and serum and bile chemistries, organ histology, animal wellbeing, and survival were monitored. RESULTS: FABAC feeding (150 mg/kg/day) caused no adverse effects in any of the animal species studied. FABAC did not influence biliary cholesterol, phospholipid, or bile-salt concentrations in mice. In hamsters, biliary cholesterol concentration decreased slightly, but effects on phospholipids and bile salts were inconsistent. In some mouse strains, FABAC supplementation increased transaminases slightly. In hamsters and rats, transaminases were mainly unaffected or even decreased. Serum alkaline phosphatase, creatinine, albumin and glucose were generally unaffected by FABAC feeding. No gross or histopathological differences between controls and FABAC-fed animals were noted in any of the organs investigated. CONCLUSIONS: C20-FABAC given at a pharmacological dose is safe and devoid of any significant toxic effects in three different animal species.
Assuntos
Bile/efeitos dos fármacos , Ácido Cólico/toxicidade , Ácidos Graxos/toxicidade , Animais , Bile/metabolismo , Glicemia/efeitos dos fármacos , Colesterol/metabolismo , Creatinina/sangue , Cricetinae , Avaliação Pré-Clínica de Medicamentos , Metabolismo dos Lipídeos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Mesocricetus , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Wistar , Albumina Sérica/efeitos dos fármacos , Especificidade da EspécieRESUMO
Gallstones, mostly cholesterol stones, affect some 15% of the population. Oral bile salts dissolve human cholesterol gallstones, but with low efficacy, and surgery remains the main therapeutic option. Fatty acid bile acid conjugates (FABACs) were shown to prevent formation of cholesterol gallstones in experimental animals. The aim of this study was to test whether these compounds could dissolve preexisting cholesterol gallstones via oral administration. Inbred, gallstone-susceptible C57J/L mice were given a lithogenic diet for 2 months, and the presence of gallstones was ascertained. The mice were then switched to a regular diet while part of them were given in addition C20-FABAC, by gavage, at a dose of 0.5 or 3 mg per animal per day. All mice tested had cholesterol gallstones after 2 months on the lithogenic diet. In study I, after 2 months on the regular diet, 3 of 4 (75%) of the controls had gallstones, whereas none of the 6 FABAC-fed animals (3 mg/d) had stones (P =.033). In study II, evaluating 2 FABAC doses, after 2 months on the regular diet, 8 of 8 (100%) of the controls had gallstones, which were found in 2 of 7 (28%) and 1 of 8 (12%) of the mice supplemented with 0.5 mg/d (P =.007) or 3 mg/d (P =.001) FABAC, respectively. On a molar basis, the dose of 0.5 mg FABAC is equivalent to 14 mg/kg/d of a bile acid. In conclusion, FABACs given orally can dissolve preexisting cholesterol gallstones in mice. This was accomplished with a dose of FABAC equivalent to the dose of bile acids used in human gallstone dissolution.