RESUMO
The objective was to compare the effect of dairy and nondairy beverages when consumed with carbohydrate at breakfast on subjective appetite, food intake (FI), and postprandial glycemia (PPG) in healthy young adults. Twenty-six healthy males and females (13 males and 13 females; 23.0 ± 2.6 years; BMI: 22.3 ± 1.5 kg/m2) participated in a randomized crossover study. They consumed nonisocaloric amounts (250 mL) of almond beverage, soy beverage, 1% fat milk, yogurt beverage, and water (control) with cereal and 120 min later, an ad libitum meal. Subjective appetite, PPG, and insulin were measured at baseline and at intervals before and after the meal at which FI was measured. Post-treatment blood glucose was lowest following soy beverage compared with all treatments but was not different from milk (p = 0.0002). There were no differences between any other treatments. However, over the first hour, PPG for all treatments was 27% lower compared with water (p < 0.0001). Milk and yogurt beverage led to the highest insulin concentrations post-treatment (p < 0.0001) but there were no differences between treatments postmeal. All treatments reduced appetite and led to lower FI at the meal compared with water, but FI was lower after milk compared with all treatments except yogurt beverage (p < 0.0001). Both dairy and nondairy beverages consumed with a high glycemic cereal at breakfast increased satiety and decreased FI compared with water with cereal. Despite higher carbohydrate content, all beverages led to similar or lower PPG than the water breakfast, but dairy beverages increased insulin more than nondairy beverages.
Assuntos
Apetite , Bebidas , Glicemia/análise , Laticínios , Ingestão de Alimentos , Período Pós-Prandial , Adulto , Índice de Massa Corporal , Desjejum , Estudos Cross-Over , Carboidratos da Dieta/administração & dosagem , Grão Comestível , Feminino , Humanos , Insulina/sangue , Masculino , Saciação , Paladar , Adulto JovemRESUMO
Recent research shows a link between vitamin intake during pregnancy and offspring health. Inadequate intakes of water-soluble vitamins during pregnancy lead to obesity and characteristics of the metabolic syndrome, concurrent with altered developments in food intake regulatory pathways. Few studies, however, have reported on the effects of fat-soluble vitamins (A, D, E, and K) on the development of food intake regulatory pathways. The majority of studies to date have focused on associations between inadequate and high intakes of folic acid and vitamin D and neurocognitive development of the offspring. Hence, the objective of this review is to present an evaluation of the role of maternal vitamins A, D, E, and K in brain development and function of neural pathways that regulate feeding behaviors. PubMed and Google Scholar were searched from 1975 through September, 2016. Most studies supporting a role for fat-soluble vitamins in regulating brain development and associated behaviors have been conducted in animal and cell models, leaving uncertain their relevance to neurocognitive development and function in humans. Nevertheless, although current research on defining the role of maternal fat-soluble vitamins in offspring's brain development is limited, it is sufficient to warrant further investigations on their impact when intake amounts during pregnancy are not only inadequate but also exceed requirements.
Assuntos
Encéfalo/efeitos dos fármacos , Comportamento Alimentar/fisiologia , Fenômenos Fisiológicos da Nutrição Pré-Natal , Vitamina A/farmacologia , Vitamina D/farmacologia , Vitamina E/farmacologia , Vitamina K/farmacologia , Animais , Regulação do Apetite , Encéfalo/crescimento & desenvolvimento , Feminino , Humanos , Gravidez , Vitaminas/farmacologiaRESUMO
Maternal intake of multivitamins or folic acid above the basal dietary requirement alters the growth and metabolic trajectory of rat offspring. We hypothesized that a modest increase in the folic acid content of maternal diets would alter the offspring's metabolic phenotype, and that these effects could be corrected by matching the folic acid content of the offspring's diet with that of the maternal diet. Female Sprague-Dawley rats were placed on a control or a 2.5× folic acid-supplemented diet prior to mating and during pregnancy and lactation. At weaning, pups from each maternal diet group were randomized to the control or to the 2.5× folic acid-supplemented diet for 25 weeks. Male pups from dams fed the folic acid-supplemented diet were 3.7% heavier than those from control-fed dams and had lower mRNA expression for leptin receptor Obrb isoform (Lepr) (11%) and Agouti-related protein (Agrp) (14%). In contrast, female pups from folic acid-supplemented dams were 5% lighter than those from control-fed dams and had lower proopiomelanocortin (Pomc) (42%), Lepr (32%), and Agrp (13%), but higher neuropeptide Y (Npy) (18%) mRNA expression. Folic acid supplementation ameliorated the alterations induced by maternal folic acid supplementation in male pups and led to the lowest insulin resistance, but the effects were smaller in female pups and led to the highest insulin resistance. In conclusion, maternal folic acid supplementation at 2.5× the control level was associated with alterations in body weight and hypothalamic gene expression in rat offspring in a sex-specific manner, and some of these effects were attenuated by postweaning folic acid supplementation.
Assuntos
Peso Corporal/efeitos dos fármacos , Suplementos Nutricionais , Ácido Fólico/administração & dosagem , Regulação da Expressão Gênica , Resistência à Insulina , Fenômenos Fisiológicos da Nutrição Materna , Proteína Relacionada com Agouti/genética , Proteína Relacionada com Agouti/metabolismo , Animais , Relação Dose-Resposta a Droga , Feminino , Ácido Fólico/sangue , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Insulina/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Necessidades Nutricionais , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico , Pró-Opiomelanocortina/genética , Pró-Opiomelanocortina/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores para Leptina/genética , Receptores para Leptina/metabolismo , Fatores Sexuais , DesmameRESUMO
Vitamin consumption prior to and during pregnancy has increased as a result of proactive recommendations by health professionals, wide availability of vitamin supplements, and liberal food-fortification policies. Folic acid, alone or in combination with other B vitamins, is the most recommended vitamin consumed during pregnancy because deficiency of this vitamin leads to birth defects in the infant. Folic acid and other B vitamins are also integral components of biochemical processes that are essential to the development of regulatory systems that control the ability of the offspring to adapt to the external environment. Although few human studies have investigated the lasting effects of high vitamin intakes during pregnancy, animal models have shown that excess vitamin supplementation during gestation is associated with negative metabolic effects in both the mothers and their offspring. This research from animal models, combined with the recognition that epigenetic regulation of gene expression is plastic, provides evidence for further examination of these relationships in the later life of pregnant women and their children.
Assuntos
Doença Crônica , Suplementos Nutricionais , Alimentos Fortificados , Fenômenos Fisiológicos da Nutrição Materna , Vitaminas/efeitos adversos , Animais , Epigênese Genética , Feminino , Humanos , Gravidez , Vitaminas/administração & dosagemRESUMO
High multivitamin (HV) content in gestational diets has long-term metabolic effects in rat offspring. These changes are associated with in utero modifications of gene expression in hypothalamic food intake regulation. However, the role of fat-soluble vitamins in mediating these effects has not been explored. Vitamin A is a plausible candidate due to its role in gene methylation. Vitamin A intake above requirements during pregnancy affects the development of neurocircuitries involved in food intake and reward regulation. Pregnant Wistar rats were fed AIN-93G diets with the following content: recommended multivitamins (1-fold multivitamins: RV), high vitamin A (10-fold vitamin A: HA) or HV with only recommended vitamin A (10-fold multivitamins, 1-fold vitamin A: HVRA). Body weight, food intake and preference, mRNA expression and DNA methylation of hippocampal dopamine-related genes were assessed in male offspring brains at different developmental windows: birth, weaning and 14weeks postweaning. HA offspring had changes in dopamine-related gene expression at all developmental windows and DNA hypermethylation in the dopamine receptor 2 promoter region compared to RV offspring. Furthermore, HA diet lowered sucrose preference but had no effect on body weight and expression of hypothalamic genes. In contrast, HVRA offspring showed only at adulthood changes in expression of hippocampal genes and a modest effect on hypothalamic genes. High vitamin A intake alone in gestational diets has long-lasting programming effects on the dopaminergic system that are further translated into decreased sucrose preference but not food intake.
Assuntos
Dopamina/metabolismo , Recompensa , Sacarose/administração & dosagem , Vitamina A/administração & dosagem , Animais , Metilação de DNA , Feminino , Gravidez , Ratos , Ratos WistarRESUMO
High intakes of multivitamins (HV) during pregnancy by Wistar rats increase food intake, body weight, and characteristics of the metabolic syndrome in male offspring. In this study, high-fat soluble vitamins were fed in combination during gestation to test the hypothesis that they partially account for the effects of the HV diet. Pregnant Wistar rats (14-16/group) were fed a recommended multivitamin diet (1-fold all vitamins) or high-fat soluble vitamin diet (HFS; 10-fold vitamins A, D, E, and K) during pregnancy. Offspring body weight, food intake, and preference as well as expression of selected genes in the hypothalamus and hippocampus were evaluated at birth, weaning, and 14 weeks postweaning. Body weight and food intake were not affected but sucrose preference decreased by 4% in those born to dams fed the HFS gestational diet. Gene expressions of the hypothalamic anorexogenic pro-opiomelanocortin (Pomc) and orexogenic neuropeptide Y (Npy) (â¼30% p = 0.008, â¼40% p = 0.007) were increased in weaning and adult rats, respectively. Hippocampal dopaminergic genes (35%-50% p < 0.05) were upregulated at birth and 14 weeks postweaning. DNA hypermethylation (2% p = 0.006) was observed in the dopamine receptor 1 (Drd1) promoter region. We conclude that a gestational diet high in vitamins A, D, E, and K does not show the effects of the HV diet on body weight or food intake but may affect the development of higher hedonic regulatory pathways associated with food preference.
Assuntos
Dieta , Preferências Alimentares/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Materna , Sacarose/administração & dosagem , Vitaminas/administração & dosagem , Animais , Animais Recém-Nascidos , Peso Corporal/efeitos dos fármacos , Metilação de DNA , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , Neuropeptídeo Y/genética , Neuropeptídeo Y/metabolismo , Gravidez , Pró-Opiomelanocortina/genética , Pró-Opiomelanocortina/metabolismo , Ratos , Ratos Wistar , Receptores de Dopamina D1/genética , Receptores de Dopamina D1/metabolismo , Sacarose/análise , Regulação para Cima , Vitamina A/administração & dosagem , Vitamina D/administração & dosagem , Vitamina E/administração & dosagem , Vitamina K/administração & dosagem , DesmameRESUMO
SCOPE: High multivitamin (HV, tenfold AIN-93G) gestational diets fed to Wistar rats increase food intake, obesity, and characteristics of metabolic syndrome in the offspring. We hypothesized that methyl vitamins, and specifically folate, in the HV gestational diet contribute to the obesogenic phenotypes consistent with their epigenetic effects on hypothalamic food intake regulatory mechanisms. METHODS AND RESULTS: Male offspring of dams fed the AIN-93G diet with high methyl vitamins (HMethyl; tenfold folate, vitamins B12, and B6) (Study 1) and HV with recommended folate (HVRF) (Study 2) were compared with those from HV and recommended vitamin (RV) fed dams. All offspring were weaned to a high fat diet for 8 wks. HMethyl diet, similar to HV, and compared to RV, resulted in higher food intake, body weight, and metabolic disturbances. Removing folate additions to the HV diet in HVRF offspring normalized the obesogenic phenotype. Methyl vitamins, and folate in HV diets, altered hypothalamic gene expression toward increased food intake concurrent with DNA methylation and leptin and insulin receptor signaling dysfunction. CONCLUSION: Methyl vitamins in HV gestational diets contribute to obesogenic phenotypes and epigenetic alterations in the hypothalamic feeding pathways in the offspring. Folate alone accounts for many of these effects.
Assuntos
Obesidade/etiologia , Efeitos Tardios da Exposição Pré-Natal , Vitaminas/efeitos adversos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Metilação de DNA , Dieta , Dieta Hiperlipídica , Ingestão de Alimentos/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Feminino , Ácido Fólico/efeitos adversos , Ácido Fólico/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Leptina/metabolismo , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Ratos Wistar , Vitamina B 12 , Vitaminas/administração & dosagem , Vitaminas/farmacologia , DesmameRESUMO
High multivitamin (10-fold, HV) and high folic acid (Fol) diets fed to pregnant Wistar rats increase body weight and characteristics of the metabolic syndrome in their offspring. Our objective was to determine the effects of a HV maternal diet on dams and whether methyl vitamins contribute to these effects. Pregnant Wistar rats were fed AIN-93G diets containing either (1) recommended multivitamins (RV, control), (2) HV, (3) HV with recommended Fol (HVRF; 1-fold Fol), or (4) RV with high methyl group vitamins (HMethyl; 10-fold Fol, vitamin B12 and B6). All groups were fed a RV diet during lactation until weaning and a RV high fat (HF; 60% fat) diet for 16 weeks post-weaning. The HV, HVRF and HMethyl diet fed dams gained 45% more weight from 2 to 15 weeks post-weaning and their weight gain (WG) was positively associated with cumulative post-weaning food intake (FI). However, only HV dams had a reduced preference for a sucrose solution, lower mesolimbic dopamine (DA) turnover in the nucleus accumbens (NAc), and higher expression of several genes involved in FI regulation in the arcuate nucleus of the hypothalamus (ARC). Energy conserving peroxisome proliferator-activated receptor (Ppar)-γ in adipose and -α in liver was also greater in these dams consistent with their WG. In conclusion, HV, HVRF and HMethyl maternal diets exacerbate maternal WG when dams are exposed to a HF diet post-weaning. However, the diets differed in their effects on central and peripheral regulatory systems of energy balance.
Assuntos
Metabolismo Energético/efeitos dos fármacos , Preferências Alimentares/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Gravidez/efeitos dos fármacos , Vitaminas/administração & dosagem , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Gordura Abdominal/efeitos dos fármacos , Fatores Etários , Animais , Animais Recém-Nascidos , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Dopamina/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Lactação/efeitos dos fármacos , Masculino , Peptídeos/genética , Peptídeos/metabolismo , Ratos , Ratos Wistar , Receptores Dopaminérgicos/genética , Receptores Dopaminérgicos/metabolismo , Fatores de Tempo , Aumento de PesoRESUMO
High multivitamin gestational diets (HV, 10-fold AIN-93G levels) increase body weight (BW) and food intake (FI) in rat offspring weaned to a recommended multivitamin (RV), but not to a HV diet. We hypothesized that high vitamin A (HA) alone, similar to HV, in post-weaning diets would prevent these effects of the HV maternal diet consistent with gene expression in FI and reward pathways. Male offspring from dams fed HV diets were weaned to a high vitamin A (HA, 10-fold AIN-93G levels), HV or RV diet for 29 weeks. BW, FI, expression of genes involved in regulation of FI and reward and global and gene-specific DNA methylation of pro-opiomelanocortin (POMC) in the hypothalamus were measured. Both HV and HA diets slowed post-weaning weight gain and modified gene expression in offspring compared to offspring fed an RV post-weaning diet. Hypothalamic POMC expression in HA offspring was not different from either HV or RV, and dopamine receptor 1 was 30% (P<.05) higher in HA vs. HV, but not different from RV group. Hippocampal expression of serotonin receptor 1A (40%, P<.01), dopamine receptor 2 (40%, P<.05) and dopamine receptor 5 (70%, P<.0001) was greater in HA vs. RV fed pups and is 40% (P<.01), 50% (P<.05) and 40% (P<.0001) in HA vs. HV pups, respectively. POMC DNA methylation was lower in HA vs. RV offspring (P<.05). We conclude that high vitamin A in post-weaning diets reduces post-weaning weight gain and FI and modifies gene expression in FI and reward pathways.
Assuntos
Dieta/veterinária , Expressão Gênica , Hipocampo/metabolismo , Vitamina A/administração & dosagem , Aumento de Peso , Animais , Metilação de DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , Pró-Opiomelanocortina/genética , Pró-Opiomelanocortina/metabolismo , Ratos , Ratos Wistar , Recomendações Nutricionais , Vitaminas/administração & dosagem , DesmameRESUMO
Rats fed gestational diets high in multivitamin or folate produce offspring of altered phenotypes. We hypothesized that female rat offspring born to dams fed a gestational diet high in folic acid (HFol) have compromised bone health and that feeding the offspring the same HFol diet attenuates these effects. Pregnant rats were fed diets with either recommended folic acid (RFol) or 10-fold higher folic acid (HFol) amounts. Female offspring were weaned to either the RFol or HFol diet for 17 weeks. HFol maternal diet resulted in lower offspring body weights (6%, P = 0.03) and, after adjusting for body weight and femoral length, smaller femoral area (2%, P = 0.03), compared to control diet. After adjustments, HFol pup diet resulted in lower mineral content (7%, P = 0.01) and density (4%, P = 0.002) of lumbar vertebra 4 without differences in strength. An interaction between folate content of the dam and pup diets revealed that a mismatch resulted in lower femoral peak load strength (P = 0.01) and stiffness (P = 0.002). However, the match in folate content failed to prevent lower weight gain. In conclusion, HFol diets fed to rat dams and their offspring affect area and strength of femurs and mineral quantity but not strength of lumbar vertebrae in the offspring.
RESUMO
Excess vitamins, especially folate, are consumed during pregnancy but later-life effects on the offspring are unknown. High multivitamin (10-fold AIN-93G, HV) gestational diets increase characteristics of metabolic syndrome in Wistar rat offspring. We hypothesized that folate, the vitamin active in DNA methylation, accounts for these effects through epigenetic modification of food intake regulatory genes. Male offspring of dams fed 10-fold folate (HFol) diet during pregnancy and weaned to recommended vitamin (RV) or HFol diets were compared with those born to RV dams and weaned to RV diet for 29 weeks. Food intake and body weight were highest in offspring of HFol dams fed the RV diet. In contrast, the HFol pup diet in offspring of HFol dams reduced food intake (7%, p = 0.02), body weight (9%, p = 0.03) and glucose response to a glucose load (21%, p = 0.02), and improved glucose response to an insulin load (20%, p = 0.009). HFol alone in either gestational or pup diet modified gene expression of feeding-related neuropeptides. Hypomethylation of the pro-opiomelanocortin (POMC) promoter occurred with the HFol pup diet. POMC-specific methylation was positively associated with glucose response to a glucose load (r = 0.7, p = 0.03). In conclusion, the obesogenic phenotype of offspring from dams fed the HFol gestational diet can be corrected by feeding them a HFol diet. Our work is novel in showing post-weaning epigenetic plasticity of the hypothalamus and that in utero programming by vitamin gestational diets can be modified by vitamin content of the pup diet.
Assuntos
Metilação de DNA/efeitos dos fármacos , Dieta , Comportamento Alimentar/efeitos dos fármacos , Ácido Fólico/farmacologia , Hipotálamo/fisiologia , Desmame , Animais , Animais Recém-Nascidos , Sequência de Bases , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Peso Corporal/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ilhas de CpG/genética , Metilação de DNA/genética , Feminino , Ácido Fólico/sangue , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Hipotálamo/efeitos dos fármacos , Masculino , Dados de Sequência Molecular , Neuropeptídeo Y/genética , Neuropeptídeo Y/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/genética , Pró-Opiomelanocortina/genética , Pró-Opiomelanocortina/metabolismo , Regiões Promotoras Genéticas/genética , Ratos , Ratos Wistar , Receptores de Serotonina/genética , Receptores de Serotonina/metabolismoRESUMO
The AIN-93G diets based on soya protein or casein were fed to pregnant Wistar rats from day 3 of gestation and compared for their effects on characteristics of the metabolic syndrome in male offspring. Pregnant rats were randomised to either a casein (C) or soya protein (S) diet (n 12) during gestation only (Expt 1) or during gestation and lactation (Expt 2). Male offspring were weaned to either a C or S diet for 9 weeks (Expt 1) or 15 weeks (Expt 2). In Expt 1, pups born to S-fed dams had higher fasting blood glucose (BG), systolic blood pressure (SBP) and diastolic blood pressure (DBP) at week 4, higher blood glucose (BG) response to a glucose administration (P < 0·001) and higher body weight (BW) at week 8 (P < 0·05). In Expt 2, consumption of the S diet throughout gestation and lactation resulted in higher BW (P < 0·05), DBP (P < 0·005) and SBP (P < 0·005) in the offspring. They also had higher homeostasis model assessment of insulin resistance (HOMA-IR; P < 0·05) and plasma homocysteine (P < 0·05) at weaning, higher fasting BG and glucose response to glucose administration (P < 0·005) at week 12 and higher HOMA-IR (P < 0·01) at week 15. Although composition of the weaning diets interacted with the diet of the dams, the latter was the dominant factor in determining metabolic outcomes in the offspring. In conclusion, the S diet, compared with the C diet, when consumed during gestation or throughout gestation and lactation increased the presence of characteristics of the metabolic syndrome in the offspring.
Assuntos
Caseínas/efeitos adversos , Lactação , Fenômenos Fisiológicos da Nutrição Materna , Síndrome Metabólica/etiologia , Síndrome Metabólica/fisiopatologia , Proteínas de Soja/efeitos adversos , Animais , Animais Recém-Nascidos , Composição Corporal , Caseínas/química , Feminino , Desenvolvimento Fetal , Glucose/metabolismo , Homocisteína/sangue , Hiperglicemia/etiologia , Hipertensão/etiologia , Resistência à Insulina , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/metabolismo , Gravidez , Distribuição Aleatória , Ratos , Ratos Wistar , Proteínas de Soja/química , Desmame , Aumento de PesoRESUMO
Conjugated linoleic acid (CLA) refers to a group of biologically active fatty acids that exhibit anticarcinogenic properties; however, the mechanism of action remains poorly understood. Caveolae are specialized plasma membrane structures that affect many facets of cancer cell function, including growth, cell signaling, and apoptosis. Therefore, one potential mechanism could be alteration of caveolae lipid composition and function. We hypothesized that CLA can alter the lipid microenvironment of caveolae and alter expression of the major caveolae-resident protein, caveolin-1. MCF-7 human breast cancer cells were treated with a vehicle control, linoleic acid (LA), or CLA for 3 days after which total cell lysate, plasma membrane, and caveolae membrane fractions were isolated. Our findings indicate that CLA readily incorporates into caveolae (Delta9cis,11trans-18:2 being the major isomer) and maybe preferentially enriched in specific phospholipid species. Furthermore, caveolin-1 localization to caveolae after treatment with CLA was decreased relative to either control- or LA-treated cells, without changes in total cellular levels of protein relative to vehicle-control treated cells. Taken together, our results suggest that further investigation of a potential therapeutic role for CLA in modulating caveolae function in breast cancer is merited.
Assuntos
Neoplasias da Mama/ultraestrutura , Cavéolas/química , Caveolina 1/análise , Ácidos Graxos/análise , Ácidos Linoleicos Conjugados/farmacologia , Fosfolipídeos/análise , Neoplasias da Mama/química , Cavéolas/efeitos dos fármacos , Cavéolas/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Ácidos Linoleicos Conjugados/metabolismo , Fosfolipídeos/metabolismoRESUMO
N-3 polyunsaturated fatty acids (PUFA), derived from marine oils, have been shown to protect against various neurological diseases. However, very little is known about their potential anticonvulsant properties. The objective of the present study was to determine whether enrichment of brain lipids with n-3 PUFA inhibits seizures induced by pentylenetetrazol. We demonstrate that increased brain levels of n-3 PUFA in transgenic fat-1 male mice, which are capable of de novo synthesis of n-3 PUFA from n-6 PUFA, increases latency to seizure onset by 45%, relative to wildtype controls (p = 0.08). Compared with wildtype littermates, transgenic fat-1 mice have significantly (p < 0.05) higher levels of docosahexaenoic acid and total n-3 PUFA in brain total lipid extracts and phospholipids. Levels of brain docosahexaenoic acid were positively correlated to seizure latency (p < 0.05). These findings demonstrate that n-3 PUFA have anticonvulsant properties and suggest the possibility of a novel, non-drug dietary approach for the treatment of epilepsy.
Assuntos
Ácidos Graxos Dessaturases/genética , Ácidos Graxos Ômega-3/metabolismo , Convulsões/metabolismo , Convulsões/fisiopatologia , Animais , Peso Corporal/genética , Encéfalo/metabolismo , Cromatografia Gasosa/métodos , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Regulação da Expressão Gênica/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pentilenotetrazol , Fosfatidilcolinas/metabolismo , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/genética , Convulsões/induzido quimicamente , Convulsões/patologia , Índice de Gravidade de DoençaRESUMO
In this study, we determined the phospholipid FA composition in the mammary gland of the transgenic Fat-1 mouse. This is the first animal model developed that can endogenously synthesize n-3 PUFA. The synthesis of n-3 PUFA is achieved through the expression of the fat-1 transgene encoding for an n-3 desaturase from Caenorhabditis elegans, which utilizes n-6 PUFA as substrate. Wild-type and Fat-1 female mice were terminated at 7 wk of age and the fifth mammary gland was removed. Lipids were extracted and phospholipids were separated by TLC and converted to FAME for analysis by GC. There was no significant change in total saturated, monounsaturated, and PUFA composition. However, there was a significant increase in total n-3 PUFA and a corresponding decrease in n-6 PUFA. The major n-3 PUFA that were enriched included 20:5n-3 and 22:6n-3. The n-6 PUFA that were reduced included 20:4n-6, 22:4n-6, and 22:5n-6. Overall, these findings demonstrate that female Fat-i mice have elevated levels of n-3 PUFA in the mammary gland. Moreover, the n-3 desaturase products are the same n-3 PUFA found in fish oil, which have been shown to have chemoprotective properties against breast cancer. Therefore, this newly developed mouse model may be highly useful for investigating molecular and cellular mechanisms by which n-3 PUFA prevents and inhibits breast cancer growth.