RESUMO
BACKGROUND: Preterm delivery and current nutrition strategies result in deficiencies of critical long-chain fatty acids (FAs) and lipophilic nutrients, increasing the risk of preterm morbidities. We sought to determine the efficacy of preventing postnatal deficits in FAs and lipophilic nutrients using an enteral concentrated lipid supplement in preterm piglets. METHODS: Preterm piglets were fed a baseline diet devoid of arachidonic acid (AA) and docosahexaenoic acid (DHA) and randomized to enteral supplementation as follows: (1) Intralipid (IL), (2) complex lipid supplement 1 (CLS1) with an AA:DHA ratio of 0.25, or (3) CLS2 with an AA:DHA ratio of 1.2. On day 8, plasma and tissue levels of FAs and lipophilic nutrients were measured and ileum histology performed. RESULTS: Plasma DHA levels decreased in the IL group by day 2. In contrast, DHA increased by day 2 compared with birth levels in both CLS1 and CLS2 groups. The IL and CLS1 groups demonstrated a continued decline in AA levels during the 8-day protocol, whereas AA levels in the CLS2 group on day 8 were comparable to birth levels. Preserving AA levels in the CLS2 group was associated with greater ileal villus height and muscular layer thickness. Lipophilic nutrients were effectively absorbed in plasma and tissues. CONCLUSIONS: Enteral administration of CLS1 and CLS2 demonstrated similar increases in DHA levels compared with birth levels. Only CLS2 maintained AA birth levels. Providing a concentrated complex lipid emulsion with an AA:DHA ratio > 1 is important in preventing postnatal AA deficits.
Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Ácidos Araquidônicos/metabolismo , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/metabolismo , Nutrição Enteral/veterinária , Ração Animal , Animais , Animais Recém-Nascidos , Ácidos Araquidônicos/deficiência , Ácidos Docosa-Hexaenoicos/deficiência , Emulsões/administração & dosagem , Nutrientes , Distribuição Aleatória , SuínosRESUMO
Steroids regulate cell proliferation, tissue development, and cell signaling via two pathways: a nuclear receptor mechanism and genome-independent signaling. Sperm activation, egg maturation, and steroid-induced anesthesia are executed via the latter pathway, the key components of which remain unknown. Here, we present characterization of the human sperm progesterone receptor that is conveyed by the orphan enzyme α/ß hydrolase domain-containing protein 2 (ABHD2). We show that ABHD2 is highly expressed in spermatozoa, binds progesterone, and acts as a progesterone-dependent lipid hydrolase by depleting the endocannabinoid 2-arachidonoylglycerol (2AG) from plasma membrane. The 2AG inhibits the sperm calcium channel (CatSper), and its removal leads to calcium influx via CatSper and ensures sperm activation. This study reveals that progesterone-activated endocannabinoid depletion by ABHD2 is a general mechanism by which progesterone exerts its genome-independent action and primes sperm for fertilization.
Assuntos
Ácidos Araquidônicos/deficiência , Endocanabinoides/deficiência , Glicerídeos/deficiência , Hidrolases/metabolismo , Progesterona/metabolismo , Receptores de Progesterona/metabolismo , Motilidade dos Espermatozoides/fisiologia , Espermatozoides/fisiologia , Adulto , Animais , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Sinalização do Cálcio , Membrana Celular/metabolismo , Fertilização , Humanos , Hidrolases/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Progesterona/farmacologia , Ratos , Ratos Wistar , Receptores de Progesterona/genética , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Adulto JovemRESUMO
Regulation of polyunsaturated fatty acid (PUFA) biosynthesis in proliferating and NGF-differentiated PC12 pheochromocytoma cells deficient in n-3 docosahexaenoic acid (DHA 22:6n-3) was studied. A dose- and time-dependent increase in eicosapentaenoic acid (EPA, 20:5n-3), docosapentaenoic acid (DPA, 22:5n-3) and DHA in phosphatidylethanolamine (PtdEtn) and phosphatidylserine (PtdSer) glycerophospholipids (GPL) via the elongation/desaturation pathway following alpha-linolenic acid (ALA, 18:3n-3) supplements was observed. That was accompanied by a marked reduction of eicosatrienoic acid (Mead acid 20:3n-9), an index of PUFA deficiency. EPA supplements were equally effective converted to 22:5n-3 and 22:6n-3. On the other hand, supplements of linoleic acid (LNA, 18:2n-6) were not effectively converted into higher n-6 PUFA intermediates nor did they impair elongation/desaturation of ALA. Co-supplements of DHA along with ALA did not interfere with 20:5n-3 biosynthesis but reduced further elongation to 22-hydrocarbon PUFA intermediates. A marked decrease in the newly synthesized 22:5n-3 and 22:6n-3 following ALA or EPA supplements was observed after nerve growth factor (NGF)-induced differentiation. NGF also inhibited the last step in 22:5n-6 formation from LNA. These results emphasize the importance of overcoming n-3 PUFA deficiency and raise the possibility that growth factor regulation of the last step in PUFA biosynthesis may constitute an important feature of neuronal phenotype acquisition.
Assuntos
Ácido Eicosapentaenoico/farmacologia , Fatores de Crescimento Neural/farmacologia , Ácido alfa-Linolênico/farmacologia , Animais , Ácidos Araquidônicos/deficiência , Diferenciação Celular/efeitos dos fármacos , Cromatografia Gasosa , Cromatografia em Camada Fina , Relação Dose-Resposta a Droga , Ácido Eicosapentaenoico/antagonistas & inibidores , Ácido Eicosapentaenoico/biossíntese , Ácidos Graxos Insaturados/antagonistas & inibidores , Ácidos Graxos Insaturados/biossíntese , Ácido Linoleico/metabolismo , Ácido Linoleico/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Células PC12 , Fosfatidiletanolaminas/biossíntese , Fosfatidilserinas/biossíntese , Ratos , Ácido alfa-Linolênico/antagonistas & inibidores , Ácido alfa-Linolênico/metabolismoRESUMO
UNLABELLED: Arachidonic (AA) and docosahexaenoic (DHA) acids are major components of endothelial, pulmonary and neuro-visual cell membranes. Preterm babies may be born with deficits of both AA and DHA. There is evidence that their endogenous anti-oxidant enzymes defence systems have only reached half the activity expected at term. Yet they are exposed to an oxygen tension greater than physiologically anticipated at this time, and the superoxide dismutase shows no evidence of significant catch-up. After birth, present enteral and parenteral feeds for the preterm baby result in a further drop of AA and DHA plasma proportions to a quarter or third of the intra-uterine expectation. At the same time, the proportion of linoleic acid (LA), the precursor for AA, rises in the plasma phosphoglycerides four-fold, thus denying the preterm infant the provision with which the placenta would have perfused the fetus to meet the very rapid demand for endothelial and neural growth. From the biochemistry it is predictable that this situation could lead to fragile cell membranes, leakage, rupture with peroxidation resulting in the formation of inflammatory and vasoconstrictive agents. CONCLUSION: The essential fatty acid content of current enteral and parenteral feeds for preterm infants is incorrectly formulated.
Assuntos
Ácidos Graxos Essenciais/análise , Alimentos Infantis/análise , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido Prematuro/crescimento & desenvolvimento , Ácidos Araquidônicos/deficiência , Ácidos Araquidônicos/metabolismo , Encéfalo/crescimento & desenvolvimento , Ácidos Docosa-Hexaenoicos/metabolismo , Metabolismo Energético , Ácidos Graxos Essenciais/deficiência , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro/metabolismo , Troca Materno-Fetal , Placenta/metabolismo , GravidezRESUMO
Leukotriene C4 is produced during hypoxic pulmonary vasoconstriction and leukotriene inhibitors preferentially inhibit the hypoxic pressor response in rats. If lipoxygenase products are important in hypoxic vasoconstriction, then an animal deficient in arachidonic acid should have a blunted hypoxic pressor response. We investigated if vascular responsiveness was decreased in vascular rings and isolated perfused lungs from rats raised on an essential fatty acid deficient diet (EFAD) compared to rats raised on a normal diet. Rats raised on the EFAD diet had decreased esterified plasma arachidonic acid and increased 5-, 8-, 11-eicosatrienoic acid compared to rats raised on the normal diet (control). Compared to the time matched responses in control isolated perfused lungs the pressor responses to angiotensin II and alveolar hypoxia were blunted in lungs from the arachidonate deficient rats. This decreased pulmonary vascular responsiveness was not affected by the addition of indomethacin or arachidonic acid to the lung perfusate. Similarly, the pulmonary artery rings from arachidonate deficient rats demonstrated decreased reactivity to norepinephrine compared to rings from control rats. In contrast, the tension increases to norepinephrine were greater in aortic rings from the arachidonate deficient rats compared to control. Stimulated lung tissue from the arachidonate deficient animals produced less slow reacting substance and platelet activating factor like material but the same amount of 6-keto-PGF1 alpha and TXB2 compared to control lungs. Thus there is an association between altered vascular responsiveness and impairment of stimulated production of slow reacting substance and platelet activating factor like material in rats raised on an EFAD diet.
Assuntos
Ácidos Araquidônicos/fisiologia , Gorduras na Dieta/administração & dosagem , Pulmão/irrigação sanguínea , Vasoconstrição , Animais , Ácido Araquidônico , Ácidos Araquidônicos/deficiência , Ácidos Araquidônicos/metabolismo , Peso Corporal , Ácidos Graxos Insaturados/sangue , Técnicas In Vitro , Pulmão/metabolismo , Masculino , Fator de Ativação de Plaquetas/metabolismo , Ratos , Ratos Endogâmicos , SRS-A/metabolismo , Vasoconstrição/efeitos dos fármacosRESUMO
Congenital malformations now represent the largest single cause of mortality in the infant of the diabetic mother. The mechanism by which diabetes exerts its teratogenic effects is not known. This study evaluated whether arachidonic acid might be involved, a possibility raised by the role of arachidonic acid in palatal elevation and fusion, processes analogous to neural tube folding and fusion. This hypothesis was tested in two animal models of diabetic embryopathy, the in vivo pregnant diabetic rat and the in vitro hyperglycemic mouse embryo culture. The subcutaneous injection of arachidonic acid (200-400 mg/kg per day) into pregnant diabetic rats during the period of organ differentiation (days 6-12) did not alter the maternal glucose concentration, the maternal weight gain, or the weight of the embryos. However, the incidence of neural tube fusion defects was reduced from 11% to 3.8% (P less than 0.005), the frequency of cleft palate was reduced from 11% to 4% (P less than 0.005), and the incidence of micrognathia was reduced from 7% to 0.8% (P less than 0.001). The addition of arachidonic acid to B10.A mouse embryos in culture also resulted in a reversal of hyperglycemia-induced teratogenesis. The teratogenic effect of D-glucose (8 mg/ml) in the medium resulted in normal neural tube fusion in only 32% of the embryos (P less than 0.006 when compared to controls). Arachidonic acid supplementation (1 or 10 micrograms/ml) produced a rate of neural tube fusion (67%) that was not significantly different from that observed in controls. The evidence presented indicates that arachidonic acid supplementation exerts a significant protective effect against the teratogenic action of hyperglycemia in both in vivo (rat) and in vitro (mouse) animal models. These data therefore suggest that the mechanism mediating the teratogenic effect of an increased glucose concentration involves a functional deficiency of arachidonic acid at a critical stage of organogenesis.
Assuntos
Ácidos Araquidônicos/deficiência , Anormalidades Congênitas/etiologia , Diabetes Mellitus Experimental/fisiopatologia , Gravidez em Diabéticas/fisiopatologia , Animais , Ácido Araquidônico , Anormalidades Congênitas/prevenção & controle , Ectogênese , Feminino , Glucose/toxicidade , Defeitos do Tubo Neural/etiologia , Defeitos do Tubo Neural/prevenção & controle , Gravidez , RatosRESUMO
Patients with multiple sclerosis had an oral load of sunflower seed oil in daily doses of 40 g during five days. This daily doses contained 27 g of linoleic acid (LA). Prior and after diet supplementation with sunflower seed oil the levels of linoleic and arachidonic acids were determined in the serum of patients. The values were expressed as relative percentages of total fatty acids. Before addition of sunflower oil to the diet the serum levels of linoleic acid (LA) and arachidonic acid (AA) were in these patients significantly lower than in controls amounting to 17.0% and 1.05% (p less than 0.001). After addition of sunflower oil the levels of LA and AA rose to 32.7% and 3.02%. The concentration of total lipids and non-esterified fatty acids in the serum increased also significantly after addition of sunflower oil. Determinations of LA and AA 10 days after withdrawal of sunflower oil showed that their levels were 23.7% and 1.95% respectively. In 2 patients addition of sunflower oil only slightly changed the very low serum LA level. These results indicate that LA and AA deficiency in patients with multiple sclerosis has the character of a non-specific dietary deficiency mainly, although the role of genetic factors controlling the levels of polyunsaturated fatty acids cannot be ruled out.