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Communication between gut microbiota and the brain is an enigma. Alterations in the gut microbial community affects enteric metabolite levels, such as short chain fatty acids (SCFAs). SCFAs have been proposed as a possible mechanism through which the gut microbiome modulate brain health and function. This study analyzed for the first time the effects of SCFAs at levels reported in human systemic circulation on SH-SY5Y human neuronal cell energy metabolism, viability, survival, and the brain lipidome. Cell and rat brain lipidomics was done using high resolution mass spectrometry (HRMS). Neuronal cells viability, survival and energy metabolism were analyzed via flow cytometer, immunofluorescence, and SeahorseXF platform. Lipidomics analysis demonstrated that SCFAs significantly remodeled the brain lipidome in vivo and in vitro. The most notable remodulation was observed in the metabolism of phosphatidylethanolamine plasmalogens, and mitochondrial lipids carnitine and cardiolipin. Increased mitochondrial mass, fragmentation, and hyperfusion occurred concomitant with the altered mitochondrial lipid metabolism resulting in decreased neuronal cell respiration, adenosine triphosphate (ATP) production, and increased cell death. This suggests SCFAs at levels observed in human systemic circulation can adversely alter the brain lipidome and neuronal cell function potentially negatively impacting brain health outcomes.
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Microbioma Gastrointestinal , Neuroblastoma , Animales , Apoptosis , Ácidos Grasos Volátiles/metabolismo , Humanos , Metabolismo de los Lípidos , RatasRESUMEN
Maternal body mass index is associated with breast milk (BM) fatty acid composition. This study investigated the effects of BM omega (n)-6:n-3 polyunsaturated fatty acids (PUFAs) from non-obese women and women with obesity on the process of adipogenesis in 3T3-L1 preadipocytes. BM samples were collected from non-obese women (BMNO) and women with obesity (BMO) at one month postpartum. The fatty acid composition was measured, and BMNO and BMO groups with the lowest (Q1) and highest (Q4) quartiles of n-6:n-3 PUFA ratios were identified. 3T3-L1 preadipocytes were differentiated in the presence or absence of BM. Lipid accumulation and the expression of genes involved in lipogenesis and lipolysis were measured. Treatment with BMNO containing high (vs. low) n-6:n-3 PUFA ratios significantly increased the mRNA expression of lipogenic genes (acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase); however, there was no effect when cells were treated with BMO (with either low or high n-6:n-3 PUFA ratios). Treatment with BMO (high n-6:n-3 PUFA ratio) caused larger lipid droplets. Our findings demonstrated that BMNO with a high n-6:n-3 PUFA ratio was associated with a higher expression of lipogenic genes, while BMO with a high n-6:n-3 PUFA ratio showed larger lipid droplets, suggesting adipocyte dysfunction. These findings may have implications in the BM-mediated programming of childhood obesity.
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The sex- and age-specific effects of omega (n)-3 polyunsaturated fatty acids (PUFA) enriched diets on brainstem and cerebellar fatty acid composition, and the expression of stearoyl-CoA desaturase (SCD)-1 and myelin basic protein (MBP) were investigated in C57BL/6 mice. Female mice were fed diets (20% fat, w/w) high or low in n-3 PUFA before mating, during pregnancy and lactation; and offspring (both males and females) were weaned onto their mother's designated diet for 16 weeks. A diet high in n-3 PUFA caused an accretion of docosahexaenoic acid in the cerebellum. Monounsaturated fatty acids increased from weaning to 16 weeks in the cerebellum. The changes in the cerebellar fatty acids were more pronounced in females, with a significant effect of diet. A diet high in n-3 PUFA increased cerebellar SCD-1 and MBP mRNA expression. These findings are novel and demonstrate that the effects of n-3 PUFA are brain region, age- and sex-specific.
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Tronco Encefálico/química , Cerebelo/química , Grasas de la Dieta/administración & dosificación , Ácidos Docosahexaenoicos/análisis , Ácidos Grasos Monoinsaturados/análisis , Ácidos Grasos Omega-3/administración & dosificación , Factores de Edad , Animales , Tronco Encefálico/efectos de los fármacos , Cerebelo/efectos de los fármacos , Grasas de la Dieta/farmacología , Ácidos Grasos Omega-3/farmacología , Femenino , Lactancia , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Animales , Proteína Básica de Mielina/genética , Embarazo , Caracteres Sexuales , Conducta Sexual Animal , Estearoil-CoA Desaturasa/genética , Regulación hacia Arriba , DesteteRESUMEN
Microorganisms (microalgae and fungi) are currently the main sources of astaxanthin; however, this carotenoid also accumulates in crustaceans, salmonids, and birds. Seafood (derived from marine animals) processing wastes are significant sources of astaxanthin and can be employed as feed and for nutraceutical applications, where shrimp wastes are the most exploited seafood industry waste employed for astaxanthin extraction. This review discusses different sources, efficient environment-friendly extraction methods employed for astaxanthin extraction, biorefinery approaches for efficient extraction and future aspects of the application of these waste sources for commercial preparation of astaxanthin complexes. It also includes a brief overview of the advantages, disadvantages, and challenges for obtaining astaxanthin from various sources and various case scenarios integrating different biorefinery approaches.
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Organismos Acuáticos/química , Carotenoides/química , Animales , Crustáceos/química , Microalgas/química , Xantófilas/química , Xantófilas/aislamiento & purificaciónRESUMEN
Regulation of cardiac fatty acid metabolism is central to the development of cardiac hypertrophy and heart failure. We investigated the effects of select fatty acids on the expression of genes involved in immediate early as well as inflammatory and hypertrophic responses in adult rat cardiomyocytes. Cardiac remodeling begins with upregulation of immediate early genes for c-fos and c-jun, followed by upregulation of inflammatory genes for nuclear factor kappa B (NF-κB) and nuclear factor of activated T-cells (NFAT). At later stages, genes involved in hypertrophic responses, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), are upregulated. Adult rat cardiomyocytes were treated with palmitic acid, a saturated fatty acid; oleic acid, a monounsaturated fatty acid; linoleic acid, a polyunsaturated fatty acid belonging to the n-6 class; and docosahexaenoic acid, a polyunsaturated fatty acid belonging to the n-3 class. Linoleic acid produced a greater increase in the mRNA expression of c-fos, c-jun, NF-κB, NFAT3, ANP, and BNP relative to palmitic acid and oleic acid. In contrast, docosahexaenoic acid caused a decrease in the expression of genes involved in cardiac hypertrophy. Our findings suggest that linoleic acid may be a potent inducer of genes involved in cardiac hypertrophy, whereas docosahexaenoic acid may be protective against the cardiomyocyte hypertrophic response.
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Ácidos Docosahexaenoicos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Ácido Linoleico/farmacología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Animales , Biomarcadores/metabolismo , Inflamación/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/genética , Masculino , Proteínas Proto-Oncogénicas c-fos/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Obesity is linked to several health complications, such as cardiovascular disease, insulin resistance, and hypertension. Dyslipidemia in obesity is one of the prime causes for health complications. We have previously shown that blue mussels (BM) are a rich source of omega (n)-3 polyunsaturated fatty acids (PUFA) and increase the mRNA expression of peroxisome-proliferator activated receptor and adiponectin, thereby inducing anti-obesity and insulin sensitizing effects in vitro. However, the in vivo effects of BM on obesity and metabolic regulation are not known. We hypothesized that dietary intake of BM will prevent weight gain and improve lipid profile of C57BL/6 mice fed a high-fat diet (HFD). Mice were fed a HFD supplemented with 5% w/w BM (BM-HFD) for 4 weeks, and then switched to a HFD for 4 weeks. Mice fed a BM-HFD showed significantly lower body weight gain and abdominal fat, compared to the HFD. Furthermore, a BM-HFD significantly reduced plasma and hepatic total and low-density lipoprotein (LDL)-cholesterol, compared to HFD. The decrease in cholesterol levels coincided with inhibition of hepatic sterol regulatory element-binding protein-2 and HMG-CoA reductase mRNA expression, and an increase in LDL-receptor gene expression in the BM-HFD group, compared to the HFD group. In conclusion, our findings have established that BM reduces body weight gain in mice. BM may have potential to lower cholesterol levels by inhibiting cholesterol synthesis, thereby protecting against obesity and perhaps heart disease.
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Fármacos Antiobesidad/uso terapéutico , Anticolesterolemiantes/uso terapéutico , Mezclas Complejas/uso terapéutico , Suplementos Dietéticos , Hipercolesterolemia/prevención & control , Mytilus edulis/química , Obesidad/prevención & control , Adiposidad , Animales , Fármacos Antiobesidad/efectos adversos , Anticolesterolemiantes/efectos adversos , Biomarcadores/sangre , LDL-Colesterol/sangre , Mezclas Complejas/efectos adversos , Dieta Alta en Grasa/efectos adversos , Suplementos Dietéticos/efectos adversos , Liofilización , Regulación de la Expresión Génica , Hidroximetilglutaril-CoA Reductasas/química , Hidroximetilglutaril-CoA Reductasas/genética , Hidroximetilglutaril-CoA Reductasas/metabolismo , Hipercolesterolemia/sangre , Hipercolesterolemia/etiología , Hipercolesterolemia/metabolismo , Resistencia a la Insulina , Hígado/enzimología , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BL , Obesidad/sangre , Obesidad/etiología , Obesidad/metabolismo , Distribución Aleatoria , Receptores de LDL/agonistas , Receptores de LDL/genética , Receptores de LDL/metabolismo , Proteína 2 de Unión a Elementos Reguladores de Esteroles/antagonistas & inhibidores , Proteína 2 de Unión a Elementos Reguladores de Esteroles/genética , Proteína 2 de Unión a Elementos Reguladores de Esteroles/metabolismoRESUMEN
High fat-high sucrose (HF-HS) diet, known as the western diet, has been shown to induce the onset of obesity via increasing metabolic inflammation, insulin resistance and adipose tissue dysfunction. Hyperleptinemia, hyperglycemia and dyslipidemia are also the primary observations of obesogenic diet induced obesity. We have previously reported anti-adipogenic and insulin sensitizing effects of blue mussels (BM) using 3T3-L1 cells. BM is a rich source of omega-3 polyunsaturated fatty acids, phytosterols and other micronutrients that has been shown to elicit benefits under obese conditions using in-vitro cell culture models. However, no studies to date have established the anti-obesity effects, safety and efficacy of BM in an in-vivo animal model. In the present study, we fed a HF-HS diet supplemented with different concentrations of BM freeze-dried powder (1.25, 2.5 and 5% w/w) to C57BL/6 mice for 12weeks. A HF-HS diet caused rapid weight gain, hyperglycemia, dyslipidemia, hyperleptinemia, and increased plasma levels of inflammatory cytokines; interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Incorporating 2.5% BM in the HF-HS diet prevented weight gain, dyslipidemia, hyperglycemia and reduced the levels of inflammatory cytokines and leptin mRNA expression. Furthermore, plasma from 2.5% BM increased cholesterol efflux capacity of J774 macrophage cells, compared to plasma from HF-HS diet. There was no effect of 1.25% BM on any tested parameters, while 5% BM was not palatable after four weeks. In conclusion, our findings have established the efficacy and safety of BM using C57BL/6 mice, demonstrating that BM has the potential to target obesity and related complications.
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Dieta Alta en Grasa/efectos adversos , Sacarosa en la Dieta/efectos adversos , Inflamación/metabolismo , Mytilus edulis/metabolismo , Obesidad/dietoterapia , Tejido Adiposo/metabolismo , Animales , Fármacos Antiobesidad/administración & dosificación , Fármacos Antiobesidad/farmacología , Biomarcadores/sangre , Colesterol/metabolismo , Citocinas/sangre , Dieta Occidental/efectos adversos , Suplementos Dietéticos , Dislipidemias/etiología , Hiperglucemia/etiología , Inflamación/sangre , Inflamación/etiología , Insulina/sangre , Resistencia a la Insulina , Interleucina-6/sangre , Leptina/metabolismo , Macrófagos , Masculino , Enfermedades Metabólicas/etiología , Ratones , Ratones Endogámicos C57BL , Modelos Animales , ARN Mensajero/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Aumento de PesoRESUMEN
Early nutrition has critical influences on cardiovascular disease risk in adulthood. The study objectives were to evaluate the impact of low birth weight on fasting and postprandial lipid metabolism and endothelium function in Yucatan miniature pigs. Intrauterine growth-restricted (IUGR) piglets (n = 6; 3 days old, 0.73 ± 0.04 kg) were paired with normal-weight (NW) same-sex littermates (n = 6; 1.11 ± 0.05 kg) and fed milk replacer ad libitum for 4 weeks. Thereafter, all pigs were fed a standard diet ad libitum for 5 h/day with growth, intakes, and blood samples collected for 8 months. At 9 months old, pigs were surgically fitted with venous catheters and an oral fat tolerance test was performed. At 10 months old, pigs were killed and endothelium-dependent and -independent vasodilations of isolated coronary arteries were measured using wire-myographs. IUGR pigs demonstrated catch-up growth (P < 0.05) in body weight and abdominal circumference prior to sexual maturity (<7 months old) and had more (P < 0.05) subcutaneous fat at 10 months old compared with NW pigs. IUGR pigs had consistently higher fasting plasma triglyceride concentrations from 5 to 10 months old and higher liver triglyceride and total cholesterol concentrations at 10 months old (P < 0.05). The fat tolerance test revealed delayed postprandial triglyceride clearance in IUGR pigs, but no differences in plaque formation or vascular reactivity. To conclude, IUGR and early postnatal catch-up growth are associated with increased overall body fat deposition and altered triglyceride metabolism in adult Yucatan miniature swine.
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Adiposidad/fisiología , Retardo del Crecimiento Fetal/veterinaria , Metabolismo de los Lípidos/fisiología , Porcinos/crecimiento & desarrollo , Animales , Animales Recién Nacidos , Dieta , Femenino , Masculino , Porcinos EnanosRESUMEN
There is clear evidence that nutritional strategy employed during pregnancy has profound influence on the offspring health outcomes. However, the effect of the quality and the quantity of maternal fat intake on maternal metabolic profile during different stages of pregnancy and its impact on pregnancy sustainability is not known. Female C57BL/6 mice (7 weeks old) were fed diets varying in the quantity of fat (5% vs 11%) for two weeks prior to mating and throughout pregnancy. The 5% fat diet was enriched with longer chain omega (n)-3 polyunsaturated fatty acids (PUFA) from fish oil. Maternal plasma and tissues were collected before mating and during pregnancy at days 6.5, 12.5 and 18.5. Plasma lipids, glucose, insulin, progesterone and estradiol levels were measured. Cholesterol efflux capacity of maternal plasma as well as the mRNA expression of placental steroidogenic acute regulatory protein and hepatic lipogenic genes (acetyl-CoA carboxylase-1, fatty acid synthase, diacylglycerol acyltransferase-2 and stearoyl-CoA desaturase-1) was determined. Feto-placental weight and fetuses sustained throughout gestation were recorded. A low-fat maternal diet enriched with n-3 PUFA increased maternal plasma triacylglycerol and the mRNA expression of rate-limiting lipogenic enzymes, along with increasing cholesterol efflux capacity (P < 0.05), likely to meet fetal lipid demand during pregnancy. Furthermore, diet enriched with longer chain n-3 PUFA increased the maternal plasma concentration of progesterone and estradiol during pregnancy (P < 0.05), which coincides with an increase in the number of fetuses sustained till day 18.5. These novel findings may be important when designing dietary strategies to optimize reproductive capability and pregnancy outcomes.
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Fenómenos Fisiológicos Nutricionales de los Animales , Dieta con Restricción de Grasas , Aceites de Pescado/administración & dosificación , Lipogénesis , Fenómenos Fisiologicos Nutricionales Maternos , Efectos Tardíos de la Exposición Prenatal , Alimentación Animal , Animales , Glucemia/metabolismo , Colesterol/sangre , Estradiol/sangre , Femenino , Aceites de Pescado/sangre , Regulación del Desarrollo de la Expresión Génica , Regulación Enzimológica de la Expresión Génica , Edad Gestacional , Insulina/sangre , Lipogénesis/genética , Hígado/enzimología , Ratones Endogámicos C57BL , Embarazo , Resultado del Embarazo , Progesterona/sangreRESUMEN
Obesity is characterized by an increase in fat mass primarily as a result of adipocyte hypertrophy. Diets enriched in omega (n)-3 polyunsaturated fatty acids (PUFA) are suggested to reduce obesity, however, the mechanisms are not well understood. We investigated the effect of n-3 PUFA on adipocyte hypertrophy and the key genes involved in adipocyte hypertrophy. Female C57BL/6 mice were fed semi-purified diets (20 % w/w fat) containing high n-3 PUFA before mating, during pregnancy, and until weaning. Male and female offspring were continued on high n-3 PUFA (10 % w/w), medium n-3 PUFA (4 % w/w), or low n-3 PUFA (2 % w/w) diet for 16 weeks postweaning. Adipocyte area was quantified using microscopy, and gonadal mRNA expression of acyl CoA:diacylglycerol acyltransferase-2 (DGAT-2), fatty acid binding protein-4 (FABP-4) and leptin were measured. The high n-3 PUFA group showed higher levels of total n-3 PUFA in gonadal TAG compared to the medium and low n-3 PUFA groups (P < 0.001). The high n-3 PUFA male group had a lower adipocyte area compared to the medium and low n-3 PUFA group (P < 0.001); however, no difference was observed in females. The high n-3 PUFA male group showed lower mRNA expression of FABP-4, DGAT-2 and leptin compared to the low n-3 PUFA group, with no difference in females. Plasma lipid levels were lower in the high n-3 PUFA group compared to the other groups. Our findings show for the first time that n-3 PUFA prevents adipocyte hypertrophy by downregulating FABP-4, DGAT-2 and leptin; the effects are however sex-specific.
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Adipocitos/efectos de los fármacos , Diacilglicerol O-Acetiltransferasa/metabolismo , Suplementos Dietéticos , Regulación hacia Abajo/efectos de los fármacos , Proteínas de Unión a Ácidos Grasos/metabolismo , Ácidos Grasos Omega-3/farmacología , Caracteres Sexuales , Adipocitos/metabolismo , Adipocitos/patología , Animales , Ácidos Grasos Omega-3/administración & dosificación , Femenino , Hipertrofia/prevención & control , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones ObesosRESUMEN
OBJECTIVE: To investigate whether the acetylated and propionated derivatives (LMP-09-1 and -2) of swertiamarin have anti-adipogenic effects. MATERIALS AND METHODS: 3T3-L1 pre-adipocytes were grown in Dulbecco's Modified Eagle's Medium (DMEM) containing 10% calf serum; fully confluent cells were differentiated with insulin, dexamethasone, and 3-isobutylmethylxanthine in the presence and absence of LMP-09-1 and -2 (100 µg/mL) for 10 days. Control cells received same amount of dimethylsulfoxide (DMSO). On day ten, cells were analyzed for triglycerides accumulation and the expression of genes involved in adipogenesis, lipogenesis, and lipolysis. In another set of experiment, effects of LMP-09-1 and 2 were studied for isoproterenol induced lipolysis using fully mature adipocytes. RESULTS: LMP-09-1 and -2 caused a significant (P < 0.001) reduction in intracellular triglycerides accumulation. Both LMP-09-1 and -2 significantly (P < 0.001) decreased the mRNA expression of peroxisome proliferator activated receptor-γ and acetyl-CoA carboxylase-1, and increased isoproterenol induced lipolysis in adipocytes. LMP-09-1 induced lipolysis even in the absence of isoproterenol, and also showed a significant up-regulation of carnitine palmitoyl transferase-1α and hormone sensitive lipase (HSL) gene expression. CONCLUSIONS: These findings show that swertiamarin derivatives, LMP-09-1 and -2 have a potent anti-adipogenic effect.
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Omega (n)-3 polyunsaturated fatty acids (PUFA), namely docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are known to reduce the risk of insulin resistance and ameliorate obesity-associated disorders. DHA and EPA structured in the phospholipid form possess superior biological effects compared to the triglyceride form available in fish oil. In this study, we have found that sea cucumber (SC) and blue mussel (BM) from Newfoundland and Labrador are rich sources of n-3 PUFA structured in the phospholipid form. Treatment with SC and BM methanolic extracts (250 and 100 µg mL(-1), respectively) significantly (p < 0.01) increased triglyceride accumulation in 3T3-L1 adipocytes, along with an increase in the mRNA expression of the peroxisome proliferator-activated receptor-γ (37 and 39%, respectively) and adiponectin (57 and 56%, respectively) compared with control cells (p < 0.05). Only SC extracts (250 µg mL(-1)) increased the mRNA expression of sterol regulatory element-binding protein-1 (SREBP-1). Treatment with higher concentrations of SC and BM extracts (500 and 750 µg mL(-1), respectively) significantly (p < 0.01) decreased triglyceride accumulation in 3T3-L1 cells as opposed to an increase in triglyceride accumulation at lower concentrations. This was due to inhibition of acetyl-CoA carboxylase-1 and SREBP-1 mRNA expression compared to control cells (p < 0.05). There was no effect of the extracts on the mRNA expression of hormone sensitive lipase or lipolysis, suggesting that the decrease in triglyceride accumulation at higher concentrations is not due to breakdown and release of fat. This is the first report to show that SC and BM are new sources of phospholipid bonded n-3 PUFA, with the potential to target insulin resistance and obesity.
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Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Ácidos Grasos Omega-3/farmacología , Mytilus edulis/química , Fosfolípidos/metabolismo , Pepinos de Mar/química , Células 3T3-L1 , Adiponectina/genética , Adiponectina/metabolismo , Animales , Ratones , PPAR gamma/genética , PPAR gamma/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Triglicéridos/metabolismoRESUMEN
Omega-3 (n-3) polyunsaturated fatty acids (PUFA) and neurotrophins are pivotal to the proper functioning of the central nervous system. We investigated the effects of perinatal and postweaning n-3 PUFA diets on cerebral cortical phospholipid fatty acid composition, and the expression of neurotrophins at weaning and 16 weeks postweaning of the male offspring of C57BL/6 mice. Female C57BL/6 mice were fed semi-purified diets (20%w/w fat) containing 10% (high) and 2% (low) n-3 PUFA before mating, during pregnancy, and until weaning. Offspring were studied at weaning and 16 weeks postweaning on their mother's designated diet. Cerebral cortical phospholipid fatty acids and mRNA expressions of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), cAMP response element binding protein (CREB), and TrkB were measured. The protein concentration of phosphorylated CREB (pCREB) was determined by ELISA. DHA and total n-3 PUFA were significantly higher in cortical phospholipids of the high n-3 PUFA group compared to the low n-3 PUFA group (P<0.0001), and increased significantly from weaning to 16 weeks (P<0.0001). There was a significant effect of diet (P<0.05) and age (P<0.05) on the mRNA expression of NGF. The mRNA expression of BDNF increased significantly (P<0.01) in the high n-3 PUFA group compared to the low n-3 PUFA group. The mRNA expression of TrKB was significantly higher (P<0.0001) at 16 weeks in the high n-3 PUFA group compared to the low n-3 PUFA group; however, no difference was observed at weaning. pCREB/Total CREB was higher in the high n-3 PUFA group compared to the low n-3 PUFA group (P<0.05). Our findings demonstrate that perinatal and postweaning diets high in n-3 PUFA lead to accretion of n-3 PUFA in brain cortex. We further found that n-3 PUFA upregulates the expression of neurotrophins and their target receptors in an age dependent fashion.
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Corteza Cerebral/metabolismo , Ácidos Grasos Omega-3/administración & dosificación , Regulación de la Expresión Génica , Factores de Crecimiento Nervioso/biosíntesis , Destete , Animales , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/crecimiento & desarrollo , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , EmbarazoRESUMEN
BACKGROUND: Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been shown to alleviate the symptoms of metabolic disorders, such as heart disease, diabetes, obesity and insulin resistance. Several putative mechanisms by which n-3 PUFA elicit beneficial health effects have been proposed; however, there is still a shortage of knowledge on the proteins and pathways that are regulated by n-3 PUFA. METHODS: Using two dimensional polyacrylamide gel electrophoresis (2D-PAGE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, we investigated the effects of diets high or low in n-3 PUFA on hepatic proteomic profile of C57BL/6 mice. RESULTS: The findings show for the first time that high dietary n-3 PUFA reduced the expression of regucalcin, adenosine kinase and aldehyde dehydrogenase. On the other hand, diets high in n-3 PUFA increased the expression of apolipoprotein A-I, S-adenosylmethionine synthase, fructose-1, 6-bisphosphatase, ketohexokinase, malate dehydrogenase, GTP-specific succinyl CoA synthase, ornithine aminotransferase and protein disulfide isomerase-A3. CONCLUSIONS: Our findings revealed for the first time that n-3 PUFA causes alterations in several novel functional proteins involved in regulating lipid, carbohydrate, one-carbon, citric acid cycle and protein metabolism, suggesting integrated regulation of metabolic pathways. These novel proteins are potential targets to develop therapeutic strategies against metabolic disorders.
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BACKGROUND: Omega (n)-3 polyunsaturated fatty acids (PUFA) are converted to bioactive lipid components that are important mediators in metabolic and physiological pathways; however, which bioactive compounds are metabolically active, and their mechanisms of action are still not clear. We investigated using lipidomic techniques, the effects of diets high in n-3 PUFA on the fatty acid composition of various bioactive lipids in plasma and liver. METHODOLOGY AND PRINCIPAL FINDINGS: Female C57BL/6 mice were fed semi-purified diets (20% w/w fat) containing varying amounts of n-3 PUFA before mating, during gestation and lactation, and until weaning. Male offspring were continued on their mothers' diets for 16 weeks. Hepatic and plasma lipids were extracted in the presence of non-naturally occurring internal standards, and tandem electrospray ionization mass spectrometry methods were used to measure the fatty acyl compositions. There was no significant difference in total concentrations of phospholipids in both groups. However, there was a significantly higher concentration of eicosapentaenoic acid containing phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and cholesteryl esters (CE) (p < 0.01) in the high n-3 PUFA group compared to the low n-3 PUFA group in both liver and plasma. Plasma and liver from the high n-3 PUFA group also had a higher concentration of free n-3 PUFA (p < 0.05). There were no significant differences in plasma concentrations of different fatty acyl species of phosphatidylethanolamine, triglycerides, sphingomyelin and ceramides. CONCLUSIONS/SIGNIFICANCE: Our findings reveal for the first time that a diet high in n-3 PUFA caused enrichment of n-3 PUFA in PC, LPC, CE and free fatty acids in the plasma and liver of C57BL/6 mice. PC, LPC, and unesterified free n-3 PUFA are important bioactive lipids, thus altering their fatty acyl composition will have important metabolic and physiological roles.
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Grasas de la Dieta/farmacología , Ácidos Grasos Omega-3/farmacología , Lípidos/sangre , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
PURPOSE: Diabetes mellitus is characterized by hyperglycemia resulting from defects in insulin secretion, action or both. The use of medicinal plants for the treatment of diabetes mellitus dates back from the Ebers papyrus of about 1550 B.C. One of the major problems with herbal drugs is that the active ingredients are not well defined. It is important to know the active components and their molecular interactions which will help to analyze their therapeutic efficacy and also to standardize the product. There are a number of medicinal plants known for their anti-diabetic effect that possess similarities in their active chemical components, e.g. iridoid and secoiridoid glycosides. METHODS: In this study, we have compared the structure of various iridoid and secoiridoid glycosides to design a novel pharmacophore. We further developed a structure-activity relationship for the inhibition of glycogen phosphorylase-a. CONCLUSION: By using docking studies, we are proposing, for the first time, that inhibition of glycogen phosphorylase-a activity is a common target for iridoids and secoiridoids to elicit anti-diabetic effects. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
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Glucógeno Fosforilasa/antagonistas & inhibidores , Hipoglucemiantes/farmacología , Glicósidos Iridoides/farmacología , Glucógeno Fosforilasa/metabolismo , Hipoglucemiantes/química , Glicósidos Iridoides/química , Simulación del Acoplamiento Molecular , Relación Estructura-ActividadRESUMEN
We have previously reported fish oil induced hyperlipidemia in BioF1B hamsters compared with Golden Syrian (GS) hamsters. Elderberry (Sambucus nigra L.) extract is abundant in anthocyanins and is believed to exert cardioprotective effects primarily by virtue of its hypolipidemic and antioxidant potential. In the current study, high-fat fish oil feeding increased oxidative stress in BioF1B hamsters compared with GS hamsters; this increase was associated with increased levels of omega-3 polyunsaturated fatty acids in plasma and liver. We then investigated whether cosupplementation with anthocyanin-rich elderberry extract would reverse fish oil induced hyperlipidemia and reduce lipid peroxidation in BioF1B hamsters. Plasma and hepatic lipids decreased significantly when hamsters were fed diets containing elderberry extract along with fish oil. Both plasma and liver thiobarbituric acid reactive substances showed significant reductions upon cosupplementation with elderberry extract in fish oil fed BioF1B hamsters. Our findings demonstrate that cosupplementation with elderberry extract reverses hyperlipidemia and lipid peroxidation observed with dietary fish oil alone in BioF1B hamsters.
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Antioxidantes/farmacología , Aceites de Pescado/farmacología , Hiperlipidemias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Sambucus/metabolismo , Animales , Antioxidantes/metabolismo , Cricetinae , Suplementos Dietéticos , Modelos Animales de Enfermedad , Ácidos Grasos Omega-3/metabolismo , Aceites de Pescado/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Extractos Vegetales/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
AIM: Fish-oil omega-3 polyunsaturated fatty acids (n-3 PUFAs) are mostly esterified to the sn-2 position of triglycerides, while in seal-oil triglycerides, these are mostly esterified to the sn-1 and -3 positions. We investigated whether fish-oil and seal-oil feeding has a different effect on the regulation of lipid metabolism and oxidative stress in BioF1B hamsters. METHODS: BioF1B hamsters were fed high fat diets rich in fish-oil or seal-oil for 4 weeks, and fasted for 14 hours prior to blood and tissue collection. RESULTS: Plasma and hepatic lipids and lipid peroxidation levels were significantly lower in seal-oil-fed hamsters as compared to those fed fish-oil. There was a selective hindrance of clearance of lipids in fish-oil-fed hamsters as reflected by higher levels of plasma apoB48. CONCLUSION: Differences in the fatty acid composition and positional distribution of n-3 PUFAs in triglycerides of fish-oil and seal-oil are suggested to trigger metabolic differences.