RESUMO
Prevention of ischemia-reperfusion liver injury is achieved by a combined omega-3 and thyroid hormone (T3 ) protocol, which may involve peroxisome-proliferator activated receptor-α (PPAR-α)-fibroblast growth factor 21 (FGF21) signaling supporting energy requirements. Combined docosahexaenoic acid (DHA; daily doses of 300 mg/kg for 3 days) plus 0.05 mg T3 /kg given to fed rats elicited higher hepatic DHA contents and serum T3 levels, increased PPAR-α mRNA and its DNA binding, with higher mRNA expression of the PPAR-α target genes for carnitine-palmitoyl transferase 1α, acyl-CoA oxidase, and 3-hydroxyl-3-methylglutaryl-CoA synthase 2, effects that were mimicked by 0.1 mg T3 /kg given alone or by the PPAR-α agonist WY-14632. Under these conditions, the mRNA expression of retinoic X receptor-α (RXR-α) is also increased, with concomitant elevation of the hepatic mRNA and protein FGF21 levels and those of serum FGF21. It is concluded that PPAR-α-FGF21 induction by DHA combined with T3 may involve ligand activation of PPAR-α by DHA and enhanced expression of PPAR-α by T3 , with consequent upregulation of the FGF21 that is controlled by PPAR-α. Considering the beneficial effects of PPAR-α-FGF21 signaling on carbohydrate and lipid metabolism, further investigations are required to clarify its potential therapeutic applications in human metabolic disorders. © 2016 BioFactors, 42(6):638-646, 2016.
Assuntos
Ácidos Docosa-Hexaenoicos/farmacologia , Fatores de Crescimento de Fibroblastos/metabolismo , Fígado/metabolismo , PPAR alfa/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Tri-Iodotironina/farmacologia , Animais , Ácidos Docosa-Hexaenoicos/farmacocinética , Ácidos Docosa-Hexaenoicos/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Fatores de Crescimento de Fibroblastos/genética , Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , PPAR alfa/genética , Ratos Sprague-Dawley , Receptor X Retinoide alfa/genética , Receptor X Retinoide alfa/metabolismo , Transdução de Sinais , Ativação Transcricional , Tri-Iodotironina/farmacocinética , Tri-Iodotironina/uso terapêutico , Regulação para CimaRESUMO
BACKGROUND/AIMS: Docosahexaenoic acid (C22:6, DHA) is an omega-3 fatty acid required for the normal development of the mammalian nervous and visual system. DHA is provided by the mother during pregnancy and lactating period. Mother's DHA supplementation during pregnancy, and even before pregnancy, has been suggested. DHA can be provided by marine oils, egg's yolk phospholipids, single cell algae oils, the pure fatty acid, or by the ethyl ester derivative (DHA-EE). Another way to provide DHA can be by sn-2 docosahexaenyl monoacylglyceride (DHA-MG), obtained by the treatment of fish oil with stereospecific lipases. sn-2 Fatty acid monoacylglycerides can be more easily absorbed at the intestine than other fatty acid derivatives. METHODS: Female rats fed with a synthetic, which provided essentially no DHA, received a 40-day supplementation of either DHA-EE or DHA-MG. Plasma and erythrocyte fatty acid composition were assessed by gas chromatography at day 0 and 40 of supplementation. RESULTS: DHA-EE increased plasma and erythrocyte DHA by 15 and 11.9%, respectively, with no modification of arachidonic acid (AA) content. DHA-MG supplementation increased plasma and erythrocyte DHA by 24 and 23.8%, respectively, but reduced AA by 5.5 and 3%, respectively. CONCLUSIONS: We conclude that in the rat, DHA-MG supplementation allows a higher plasma and erythrocyte DHA content than DHA-EE with minor modification of AA content.
Assuntos
Gorduras Insaturadas na Dieta/administração & dosagem , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/sangue , Membrana Eritrocítica/química , Animais , Ácido Araquidônico/análise , Cromatografia Gasosa , Gorduras Insaturadas na Dieta/metabolismo , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/farmacocinética , Ácidos Graxos Insaturados/sangue , Feminino , Absorção Intestinal , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
BACKGROUND: Maternal omega-3 fatty acid supplementation has been suggested to provide docosahexaenoic acid (DHA) for the normal brain development during gestation. DHA can be given as such (preformed) or through the omega-3 precursor alpha-linolenic acid (LNA) which is transformed into DHA by elongation and desaturation reactions. Western diet provides low amounts of LNA and DHA; therefore, supplementation with these omega-3 fatty acids has been suggested for pregnant women. However, the bioequivalence of LNA ingestion to DHA supplementation has not been established. METHODS: Recently weaning female Wistar rats were fed a diet containing a small amount of LNA and no DHA. The animals were daily supplemented 40 days before mating, during pregnancy, and until delivery with 60 mg/kg of LNA or 6 mg/kg of DHA dissolved in coconut oil. Fatty acids were given as ethyl ester derivatives. Controls received coconut oil. The fatty acid composition of blood plasma, erythrocytes, liver, visceral adipose tissue, and brain segments (frontal cortex, hippocampus, and cerebellum) was analyzed. Brain segments obtained from 16- and 19-day-old fetuses and from 2- and 21-day-old rats were also analyzed for fatty acid composition. RESULTS: Supplementation with LNA and DHA induced a similar accretion of DHA in plasma, erythrocytes, liver, and brain segments of the mothers. The adipose tissue showed a higher DHA accretion after DHA-supplementation. The DHA accretion in frontal cortex, hippocampus, and cerebellum obtained from the fetuses and the newborn rats was similar when the mothers were supplemented with LNA and DHA. Our results show that under our experimental conditions a similar accretion of DHA in the different tissues of the mothers and in the brain segments of fetuses and newborn rats is obtained after LNA and DHA supplementation. CONCLUSION: LNA and DHA, at the amounts given in this study, show a similar bioequivalence for DHA accretion in different tissues of the mother and in brain segments of fetuses and newborn rats.
Assuntos
Animais Recém-Nascidos/metabolismo , Encéfalo/embriologia , Encéfalo/metabolismo , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido alfa-Linolênico/administração & dosagem , Administração Oral , Animais , Química Encefálica , Ácidos Docosa-Hexaenoicos/farmacocinética , Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Desenvolvimento Embrionário e Fetal/fisiologia , Feminino , Gravidez , Distribuição Aleatória , Ratos , Ácido alfa-Linolênico/farmacocinéticaRESUMO
Hyperhomocysteinemia in association with vitamin B(12) deficiency, and increased platelet aggregation, probably due to dietary lack of n-3 fatty acids, constitute cardiovascular risk factors frequently observed in vegetarians. We tested if administration of vitamin B(12) normalizes the concentration of total plasma homocysteine, and if intake of eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) fatty acids modulates platelet function in a population of lactoovovegetarians. One week after a single intramuscular injection of cyanocobalamin (10000 microg) in 18 individuals, serum vitamin B(12) increased from 149+/-63 pg/mL to 532+/-204 pg/mL (p<0.0001) and total tHcy dropped from 12.4+/-4.7 to 7.9+/-3.1 micromol/L (p<0. 0001). Ten of fourteen of these vegetarians completed an 8-week supplementation with 700 mg/day of each eicosapentaenoic and docosahexaenoic acids. Increased incorporation of these fatty acids into plasma lipids was observed in all of them, together with a significant reduction in maximum percentage or slope of platelet aggregation with all the agonists tested (ADP, epinephrin, collagen, arachidonic acid). No significant change in bleeding time was observed after n-3 fatty acid trial. Supplementation with vitamin B(12) and n-3 fatty acids corrects hyperhomocysteinemia and reduces platelet reactivity to agonists in vegetarians. Whether this supplementation improves the already reduced cardiovascular morbidity and mortality associated with vegetarian diet has yet to be demonstrated.
Assuntos
Doenças Cardiovasculares/dietoterapia , Dieta Vegetariana/efeitos adversos , Adulto , Doenças Cardiovasculares/prevenção & controle , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/sangue , Ácidos Docosa-Hexaenoicos/farmacocinética , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/sangue , Ácido Eicosapentaenoico/farmacocinética , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-3/farmacocinética , Feminino , Humanos , Hiper-Homocisteinemia/tratamento farmacológico , Hiper-Homocisteinemia/etiologia , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacos , Fatores de Risco , Vitamina B 12/administração & dosagem , Vitamina B 12/sangue , Vitamina B 12/farmacocinéticaRESUMO
El ácido docosahexaenoico (C22:6, omega-3,DHA) es un ácido graso poliinsaturado de cadena larga que forma parte de los fosfolípidos de las membranas de los tejidos de mamíferos superiores, especialmente del tejido nervioso y visual, donde constituye más del 60 por ciento de la composición lipídica. El adulto humano sintetiza el DHA a partir del precursor ácido alfa-linolénico en cantidad suficiente para suplir los requerimientos metabólicos. El mayor requerimiento de DHA ocurre durante la vida intrauterina y en los primeros meses de vida, etapas en las consolida la formación del tejido nervioso y visual. La madre aporta el DHA requerido por el feto a través del transporte placentario durante el embarazo y a través de la leche después del parto. Se estima que el feto y el recién nacido no son capaces de suplir sus requerimientos nutricionales de DHA, por lo cual se les considera como grupos vulnerables a la deficiencia del ácido graso, siendo el aporte materno imprecindible. La embarazada utiliza sus reservas de DHA para transferírselas al feto, por lo cual este estado fisiológico constituye otra condición de vulnerabilidad a la deficiencia nutricional de DHA. La ausencia de lactancia materna post-parto y durante los primeros meses de vida puede producir una carencia fisiológica de DHA que conduce a transtornos en el desarrollo del sistema nervioso y de la función visual del lactante, afectando potencialmente su capacidad congenita y la agudeza visual. La leche de vaca no reemplaza a la leche materna en cuanto al aporte de DHA. Se recomienda que las fórmulas de reemplazo contengan DHA en cantidad similar al de la leche materna. Actualmente existen productos para la alimentación de recién nacido que en su formulación incorporan DHA y otros ácidos grasos requeridos por estos individuos
Assuntos
Humanos , Feminino , Gravidez , Recém-Nascido , /biossíntese , Aleitamento Materno , Ácidos Docosa-Hexaenoicos/farmacologia , /farmacologia , Ácidos Docosa-Hexaenoicos/química , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Docosa-Hexaenoicos/farmacocinética , Alimentos Formulados , Troca Materno-Fetal , Tecido Nervoso/crescimento & desenvolvimento , Nervo Óptico/crescimento & desenvolvimento , Nutrição Materna , Nutrição do Lactente , Necessidades NutricionaisRESUMO
The effect of docosahexaenoic acid (DHA) on neuronal survival was studied in cultured cells isolated from newborn rat retina. In vivo, the content of DHA in the retina increased nearly fourfold from days 2 to 12 after birth, whereas in retinal cells in culture it remained constant. Unlike amacrine cells, the photoreceptor cells in control cultures underwent a selective degeneration, starting at day 7, that led to their massive death by day 11. The addition of DHA at day 7 led to its active incorporation by the cultures, increasing from 6 to 21% of total fatty acids in cell lipids, and completely prevented photoreceptor cell death. When other fatty acids were tested, both neuronal fatty acid composition and photoreceptor death were the same as in control cultures. These results indicate that DHA is specifically required for the survival of retinal photoreceptors.