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1.
J Nutr ; 150(11): 2900-2911, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-32937654

RESUMO

BACKGROUND: Soybean lecithin, a plant-based emulsifier widely used in food, is capable of modulating postprandial lipid metabolism. With arising concerns of sustainability, alternative sources of vegetal lecithin are urgently needed, and their metabolic effects must be characterized. OBJECTIVES: We evaluated the impact of increasing doses of rapeseed lecithin (RL), rich in essential α-linolenic acid (ALA), on postprandial lipid metabolism and ALA bioavailability in lymph-cannulated rats. METHODS: Male Wistar rats (8 weeks old) undergoing a mesenteric lymph duct cannulation were intragastrically administered 1 g of an oil mixture containing 4% ALA and 0, 1, 3, 10, or 30% RL (5 groups). Lymph fractions were collected for 6 h. Lymph lipids and chylomicrons (CMs) were characterized. The expression of genes implicated in intestinal lipid metabolism was determined in the duodenum at 6 h. Data was analyzed using either sigmoidal or linear mixed-effects models, or one-way ANOVA, where appropriate. RESULTS: RL dose-dependently increased the lymphatic recovery (AUC) of total lipids (1100 µg/mL·h per additional RL%; P = 0.010) and ALA (50 µg/mL·h per additional RL%; P = 0.0076). RL induced a faster appearance of ALA in lymph, as evidenced by the exponential decrease of the rate of appearance of ALA with RL (R2 = 0.26; P = 0.0064). Although the number of CMs was unaffected by RL, CM diameter was increased in the 30%-RL group, compared to the control group (0% RL), by 86% at 3-4 h (P = 0.065) and by 81% at 4-6 h (P = 0.0002) following administration. This increase was positively correlated with the duodenal mRNA expression of microsomal triglyceride transfer protein (Mttp; ρ= 0.63; P = 0.0052). The expression of Mttp and secretion-associated, ras-related GTPase 1 gene homolog B (Sar1b, CM secretion), carnitine palmitoyltransferase IA (Cpt1a) and acyl-coenzyme A oxidase 1 (Acox1, beta-oxidation), and fatty acid desaturase 2 (Fads2, bioconversion of ALA into long-chain n-3 PUFAs) were, respectively, 49%, 29%, 74%, 48%, and 55% higher in the 30%-RL group vs. the control group (P < 0.05). CONCLUSIONS: In rats, RL enhanced lymphatic lipid output, as well as the rate of appearance of ALA, which may promote its subsequent bioavailability and metabolic fate.


Assuntos
Brassica napus/química , Lecitinas/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Linfa/química , Linfa/metabolismo , Ácido alfa-Linolênico/metabolismo , Animais , Disponibilidade Biológica , Lecitinas/química , Ratos , Ácido alfa-Linolênico/química
2.
Food Chem ; 251: 1-8, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29426414

RESUMO

Lipid transmethylation methods described in the literature are not always evaluated with care so to insure that the methods are effective, especially on food matrix or biological samples containing polyunsaturated fatty acid (PUFA). The aim of the present study was to select a method suitable for all lipid species rich in long chain n-3 PUFA. Three published methods were adapted and applied on individual lipid classes. Lipid (trans)methylation efficiency was characterized in terms of reaction yield and gas chromatography (GC) analysis. The acid-catalyzed method was unable to convert triglycerides and sterol esters, while the method using an incubation at a moderate temperature was ineffective on phospholipids and sterol esters. On the whole only the method using sodium methoxide and sulfuric acid was effective on lipid classes taken individually or in a complex medium. This study highlighted the use of an appropriate (trans)methylation method for insuring an accurate fatty acid composition.


Assuntos
Ácidos Graxos Ômega-3/análise , Lipídeos/análise , Lipídeos/química , Animais , Cromatografia Gasosa/métodos , Ácidos Graxos Ômega-3/química , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Insaturados/análise , Humanos , Metanol/química , Metilação , Fosfolipídeos/análise , Fosfolipídeos/química , Ratos , Ácidos Sulfúricos/química , Triglicerídeos/química
3.
Eur J Med Chem ; 123: 834-848, 2016 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-27543878

RESUMO

Based on a previous study and in silico molecular docking experiments, we have designed and synthesized a new series of ten 5-Alkoxy-N-3-(3-PhenoxyPhenyl)-1,3,4-Oxadiazol-2(3H)-one derivatives (RmPPOX). These molecules were further evaluated as selective and potent inhibitors of mammalian digestive lipases: purified dog gastric lipase (DGL) and guinea pig pancreatic lipase related protein 2 (GPLRP2), as well as porcine (PPL) and human (HPL) pancreatic lipases contained in porcine pancreatic extracts (PPE) and human pancreatic juices (HPJ), respectively. These compounds were found to strongly discriminate classical pancreatic lipases (poorly inhibited) from gastric lipase (fully inhibited). Among them, the 5-(2-(Benzyloxy)ethoxy)-3-(3-PhenoxyPhenyl)-1,3,4-Oxadiazol-2(3H)-one (BemPPOX) was identified as the most potent inhibitor of DGL, even more active than the FDA-approved drug Orlistat. BemPPOX and Orlistat were further compared in vitro in the course of test meal digestion, and in vivo with a mesenteric lymph duct cannulated rat model to evaluate their respective impacts on fat absorption. While Orlistat inhibited both gastric and duodenal lipolysis and drastically reduced fat absorption in rats, BemPPOX showed a specific action on gastric lipolysis that slowed down the overall lipolysis process and led to a subsequent reduction of around 55% of the intestinal absorption of fatty acids compared to controls. All these data promote BemPPOX as a potent candidate to efficiently regulate the gastrointestinal lipolysis, and to investigate its link with satiety mechanisms and therefore develop new strategies to "fight against obesity".


Assuntos
Digestão/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Mucosa Gástrica/metabolismo , Absorção Intestinal/efeitos dos fármacos , Lipólise/efeitos dos fármacos , Oxidiazóis/farmacologia , Estômago/efeitos dos fármacos , Animais , Cães , Cobaias , Humanos , Cinética , Lipase/antagonistas & inibidores , Lipase/química , Lipase/metabolismo , Masculino , Simulação de Acoplamento Molecular , Conformação Proteica , Ratos
4.
Br J Nutr ; 112(11): 1805-18, 2014 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-25331622

RESUMO

n-3 Long-chain PUFA (n-3 LC-PUFA), particularly EPA and DHA, play a key role in the maintenance of brain functions such as learning and memory that are impaired during ageing. Ageing is also associated with changes in the DHA content of brain membranes that could contribute to memory impairment. Limited studies have investigated the effects of ageing and n-3 LC-PUFA supplementation on both blood and brain fatty acid compositions. Therefore, we assessed the relationship between fatty acid contents in plasma and erythrocyte membranes and those in the hippocampus, striatum and cerebral cortex during ageing, and after a 5-month period of EPA/DHA supplementation in rats. In the blood, ageing was associated with an increase in plasma DHA content, whereas the DHA content remained stable in erythrocyte membranes. In the brain, ageing was associated with a decrease in DHA content, which was both region-specific and phospholipid class-specific. In EPA/DHA-supplemented aged rats, DHA contents were increased both in the blood and brain compared with the control rats. The present results demonstrated that n-3 LC-PUFA level in the plasma was not an accurate biomarker of brain DHA status during ageing. Moreover, we highlighted a positive relationship between the DHA levels in erythrocyte phosphatidylethanolamine (PE) and those in the hippocampus and prefrontal cortex in EPA/DHA-supplemented aged rats. Within the framework of preventive dietary supplementation to delay brain ageing, these results suggest the possibility of using erythrocyte PE DHA content as a reliable biomarker of DHA status in specific brain regions.


Assuntos
Envelhecimento/sangue , Envelhecimento/metabolismo , Encéfalo/metabolismo , Ácidos Docosa-Hexaenoicos/sangue , Envelhecimento/psicologia , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Córtex Cerebral/metabolismo , Corpo Estriado/metabolismo , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/metabolismo , Membrana Eritrocítica/efeitos dos fármacos , Ácidos Graxos/sangue , Ácidos Graxos/metabolismo , Ácidos Graxos Ômega-3/administração & dosagem , Hipocampo/metabolismo , Masculino , Memória/fisiologia , Fosfatidilcolinas/sangue , Fosfatidilcolinas/metabolismo , Fosfatidiletanolaminas/sangue , Fosfatidiletanolaminas/metabolismo , Ratos , Ratos Wistar
5.
Br J Nutr ; 105(7): 1026-35, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21080982

RESUMO

The bioavailability of α-linolenic acid (ALA) from flaxseed oil in an emulsified form v. a non-emulsified form was investigated by using two complementary approaches: the first one dealt with the characterisation of the flaxseed oil emulsion in in vitro gastrointestinal-like conditions; the second one compared the intestinal absorption of ALA in rats fed the two forms of the oil. The in vitro study on emulsified flaxseed oil showed that decreasing the pH from 7·3 to 1·5 at the physiological temperature (37°C) induced instantaneous oil globule coalescence. Some phase separation was observed under acidic conditions that vanished after further neutralisation. The lecithin used to stabilise the emulsions inhibited TAG hydrolysis by pancreatic lipase. In contrast, lipid solubilisation by bile salts (after lipase and phospholipase hydrolysis) was favoured by preliminary oil emulsification. The in vivo absorption of ALA in thoracic lymph duct-cannulated rats fed flaxseed oil, emulsified or non-emulsified, was quantified. Oil emulsification significantly favoured the rate and extent of ALA recovery as measured by the maximum ALA concentration in the lymph (Cmax = 14 mg/ml at 3 h in the emulsion group v. 9 mg/ml at 5 h in the oil group; P < 0·05). Likewise, the area under the curve of the kinetics was significantly higher in the emulsion group (48 mg × h/ml for rats fed emulsion v. 26 mg × h/ml for rats fed oil; P < 0·05). On the whole, ALA bioavailability was improved with flaxseed oil ingested in an emulsified state. Data obtained from the in vitro studies helped to partly interpret the physiological results.


Assuntos
Gorduras na Dieta/farmacocinética , Emulsões/química , Óleo de Semente do Linho/química , Sistema Linfático/metabolismo , Ácido alfa-Linolênico/farmacocinética , Animais , Área Sob a Curva , Ácidos e Sais Biliares/metabolismo , Disponibilidade Biológica , Linho/química , Concentração de Íons de Hidrogênio , Masculino , Ratos , Ratos Wistar , Solubilidade , Temperatura , Triglicerídeos/metabolismo
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