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1.
Antioxidants (Basel) ; 13(1)2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38247527

RESUMO

The regular intake of diets high in saturated fat and sugars increases oxidative stress and has been linked to cognitive decline and premature brain aging. The cerebellum is highly vulnerable to oxidative stress and thus, obesogenic diets might be particularly detrimental to this tissue. However, the precise molecular mechanisms behind obesity-related brain damage are still not clear. Since protein carbonylation, a biomarker of oxidative stress, influences protein functions and is involved in metabolic control, the current investigation addressed the effect of long-term high-fat and high-sucrose diet intake on the cerebellum of Sprague-Dawley rats by deciphering the changes caused in the carbonylated proteome. The antioxidant effects of fish oil supplementation on cerebellar carbonylated proteins were also investigated. Lipid peroxidation products and carbonylated proteins were identified and quantified using immunoassays and 2D-LC-MS/MS in the cerebellum. After 21 weeks of nutritional intervention, the obesogenic diet selectively increased carbonylation of the proteins that participate in ATP homeostasis and glutamate metabolism in the cerebellum. Moreover, the data demonstrated that fish oil supplementation restrained carbonylation of the main protein targets oxidatively damaged by the obesogenic diet, and additionally protected against carbonylation of several other proteins involved in amino acid biosynthesis and neurotransmission. Therefore, dietary interventions with fish oils could help the cerebellum to be more resilient to oxidative damage. The results could shed some light on the effect of high-fat and high-sucrose diets on redox homeostasis in the cerebellum and boost the development of antioxidant-based nutritional interventions to improve cerebellum health.

2.
Biomed Pharmacother ; 168: 115708, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37857255

RESUMO

High daily intake of saturated fats and refined carbohydrates, which often leads to obesity and overweight, has been associated with cognitive impairment, premature brain aging and the aggravation of neurodegenerative diseases. Although the molecular pathology of obesity-related brain damage is not fully understood, the increased levels of oxidative stress induced by the diet seem to be definitively involved. Being protein carbonylation determinant for protein activity and function and a main consequence of oxidative stress, this study aims to investigate the effect of the long-term high-fat and sucrose diet intake on carbonylated proteome of the cerebral cortex of Sprague-Dawley rats. To achieve this goal, the study identified and quantified the carbonylated proteins and lipid peroxidation products in the cortex, and correlated them with biometrical, biochemical and other redox status parameters. Results demonstrated that the obesogenic diet selectively increased oxidative damage of specific proteins that participate in fundamental pathways for brain function, i.e. energy production, glucose metabolism and neurotransmission. This study also evaluated the antioxidant properties of fish oil to counteract diet-induced brain oxidative damage. Fish oil supplementation demonstrated a stronger capacity to modulate carbonylated proteome in the brain cortex. Data indicated that fish oils did not just decrease carbonylation of proteins affected by the obesogenic diet, but also decreased the oxidative damage of other proteins participating in the same metabolic functions, reinforcing the beneficial effect of the supplement on those pathways. The results could help contribute to the development of successful nutritional-based interventions to prevent cognitive decline and promote brain health.


Assuntos
Óleos de Peixe , Proteoma , Ratos , Animais , Óleos de Peixe/farmacologia , Sacarose , Ratos Sprague-Dawley , Dieta , Suplementos Nutricionais , Estresse Oxidativo , Obesidade , Córtex Cerebral , Dieta Hiperlipídica/efeitos adversos
3.
Nutrients ; 15(9)2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-37432326

RESUMO

Chlorella is a marine microalga rich in proteins and containing all the essential amino acids. Chlorella also contains fiber and other polysaccharides, as well as polyunsaturated fatty acids such as linoleic acid and alpha-linolenic acid. The proportion of the different macronutrients in Chlorella can be modulated by altering the conditions in which it is cultured. The bioactivities of these macronutrients make Chlorella a good candidate food to include in regular diets or as the basis of dietary supplements in exercise-related nutrition both for recreational exercisers and professional athletes. This paper reviews current knowledge of the effects of the macronutrients in Chlorella on physical exercise, specifically their impact on performance and recovery. In general, consuming Chlorella improves both anaerobic and aerobic exercise performance as well as physical stamina and reduces fatigue. These effects seem to be related to the antioxidant, anti-inflammatory, and metabolic activity of all its macronutrients, while each component of Chlorella contributes its bioactivity via a specific action. Chlorella is an excellent dietary source of high-quality protein in the context of physical exercise, as dietary proteins increase satiety, activation of the anabolic mTOR (mammalian Target of Rapamycin) pathway in skeletal muscle, and the thermic effects of meals. Chlorella proteins also increase intramuscular free amino acid levels and enhance the ability of the muscles to utilize them during exercise. Fiber from Chlorella increases the diversity of the gut microbiota, which helps control body weight and maintain intestinal barrier integrity, and the production of short-chain fatty acids (SCFAs), which improve physical performance. Polyunsaturated fatty acids (PUFAs) from Chlorella contribute to endothelial protection and modulate the fluidity and rigidity of cell membranes, which may improve performance. Ultimately, in contrast to several other nutritional sources, the use of Chlorella to provide high-quality protein, dietary fiber, and bioactive fatty acids may also significantly contribute to a sustainable world through the fixation of carbon dioxide and a reduction of the amount of land used to produce animal feed.


Assuntos
Chlorella , Animais , Nutrientes , Aminoácidos Essenciais , Fibras na Dieta/farmacologia , Exercício Físico , Mamíferos
4.
Stroke ; 54(7): 1875-1887, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37226775

RESUMO

BACKGROUND: Respiratory and urinary tract infections are frequent complications in patients with severe stroke. Stroke-associated infection is mainly due to opportunistic commensal bacteria of the microbiota that may translocate from the gut. We investigated the mechanisms underlying gut dysbiosis and poststroke infection. METHODS: Using a model of transient cerebral ischemia in mice, we explored the relationship between immunometabolic dysregulation, gut barrier dysfunction, gut microbial alterations, and bacterial colonization of organs, and we explored the effect of several drug treatments. RESULTS: Stroke-induced lymphocytopenia and widespread colonization of lung and other organs by opportunistic commensal bacteria. This effect correlated with reduced gut epithelial barrier resistance, and a proinflammatory sway in the gut illustrated by complement and nuclear factor-κB activation, reduced number of gut regulatory T cells, and a shift of gut lymphocytes to γδT cells and T helper 1/T helper 17 phenotypes. Stroke increased conjugated bile acids in the liver but decreased bile acids and short-chain fatty acids in the gut. Gut fermenting anaerobic bacteria decreased while opportunistic facultative anaerobes, notably Enterobacteriaceae, suffered an expansion. Anti-inflammatory treatment with a nuclear factor-κB inhibitor fully abrogated the Enterobacteriaceae overgrowth in the gut microbiota induced by stroke, whereas inhibitors of the neural or humoral arms of the stress response were ineffective at the doses used in this study. Conversely, the anti-inflammatory treatment did not prevent poststroke lung colonization by Enterobacteriaceae. CONCLUSIONS: Stroke perturbs homeostatic neuro-immuno-metabolic networks facilitating a bloom of opportunistic commensals in the gut microbiota. However, this bacterial expansion in the gut does not mediate poststroke infection.


Assuntos
Microbioma Gastrointestinal , Pneumonia , Acidente Vascular Cerebral , Camundongos , Animais , NF-kappa B , Bactérias/genética , Acidente Vascular Cerebral/complicações , Pulmão
5.
Antioxidants (Basel) ; 12(3)2023 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-36978999

RESUMO

Obesity has been recognized as a major risk factor for chronic kidney disease, insulin resistance being an early common metabolic feature in patients suffering from this syndrome. This study aims to investigate the mechanism underlying the induction of kidney dysfunction and the concomitant onset of insulin resistance by long-term high-fat and sucrose diet feeding in Sprague Dawley rats. To achieve this goal, our study analyzed renal carbonylated protein patterns, ectopic lipid accumulation and fatty acid profiles and correlated them with biometrical and biochemical measurements and other body redox status parameters. Rats fed the obesogenic diet developed a prediabetic state and incipient kidney dysfunction manifested in increased plasma urea concentration and superior levels of renal fat deposition and protein carbonylation. An obesogenic diet increased renal fat by preferentially promoting the accumulation of saturated fat, arachidonic, and docosahexaenoic fatty acids while decreasing oleic acid. Renal lipotoxicity was accompanied by selectively higher carbonylation of proteins involved in the blood pH regulation, i.e., bicarbonate reclamation and synthesis, amino acid, and glucose metabolisms, directly related to the onset of insulin resistance. This study also tested the combination of antioxidant properties of fish oil with the anti-diabetic properties of buckwheat D-Fagomine to counteract diet-induced renal alterations. Results demonstrated that bioactive compounds combined attenuated lipotoxicity, induced more favorable lipid profiles and counteracted the excessive carbonylation of proteins associated with pH regulation in the kidneys, resulting in an inhibition of the progression of the prediabetes state and kidney disease.

6.
Nutrients ; 14(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36364917

RESUMO

The goal of this work is to explore if the changes induced by d-fagomine in the gut microbiota are compatible with its effect on body weight and inflammation markers in rats. Methods: Sprague Dawley rats were fed a standard diet supplemented with d-fagomine (or not, for comparison) for 6 months. The variables measured were body weight, plasma mediators of inflammation (hydroxyeicosatetraenoic acids, leukotriene B4, and IL-6), and the concentration of acetic acid in feces and plasma. The composition and diversities of microbiota in cecal content and feces were estimated using 16S rRNA metabarcoding and high-throughput sequencing. We found that after just 6 weeks of intake d-fagomine significantly reduced body weight gain, increased the plasma acetate concentration, and reduced the plasma concentration of the pro-inflammatory biomarkers' leukotriene B4, interleukin 6 and 12 hydroxyeicosatetraenoic acids. These changes were associated with a significantly increased prevalence of Bacteroides and Prevotella feces and increased Bacteroides, Prevotella, Clostridium, and Dysgonomonas while reducing Anaerofilum, Blautia, and Oribacterium in cecal content. In conclusion, d-fagomine induced changes in the composition and diversity of gut microbiota similar to those elicited by dietary fiber and compatible with its anti-inflammatory and body-weight-reducing effects.


Assuntos
Microbioma Gastrointestinal , Ratos , Animais , RNA Ribossômico 16S/genética , Leucotrieno B4 , Ratos Sprague-Dawley , Peso Corporal , Fibras na Dieta/farmacologia , Fezes/microbiologia , Inflamação , Ácidos Hidroxieicosatetraenoicos/farmacologia
7.
Front Physiol ; 12: 673095, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135770

RESUMO

The benefits of intermittent hypobaric hypoxia (IHH) exposure for health and its potential use as a training tool are well-documented. However, since hypobaric hypoxia and cold are environmental factors always strongly associated in the biosphere, additive or synergistic adaptations could have evolved in animals' genomes. For that reason, the aim of the present study was to investigate body composition and hematological and muscle morphofunctional responses to simultaneous intermittent exposure to hypoxia and cold. Adult male rats were randomly divided into four groups: (1) control, maintained in normoxia at 25°C (CTRL); (2) IHH exposed 4 h/day at 4,500 m (HYPO); (3) intermittent cold exposed 4 h/day at 4°C (COLD); and (4) simultaneously cold and hypoxia exposed (COHY). At the end of 9 and 21 days of exposure, blood was withdrawn and gastrocnemius (GAS) and tibialis anterior muscles, perigonadal and brown adipose tissue, diaphragm, and heart were excised. GAS transversal sections were stained for myofibrillar ATPase and succinate dehydrogenase for fiber typing and for endothelial ATPase to assess capillarization. Hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), and glucose transporter 1 (GLUT1) from GAS samples were semi-quantified by Western blotting. COLD and HYPO underwent physiological adjustments such as higher brown adipose tissue weight and increase in blood-related oxygen transport parameters, while avoiding some negative effects of chronic exposure to cold and hypoxia, such as body weight and muscle mass loss. COHY presented an additive erythropoietic response and was prevented from right ventricle hypertrophy. Intermittent cold exposure induced muscle angiogenesis, and IHH seems to indicate better muscle oxygenation through fiber area reduction.

8.
Nutrients ; 13(2)2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33572056

RESUMO

Marine and freshwater algae and their products are in growing demand worldwide because of their nutritional and functional properties. Microalgae (unicellular algae) will constitute one of the major foods of the future for nutritional and environmental reasons. They are sources of high-quality protein and bioactive molecules with potential application in the modern epidemics of obesity and diabetes. They may also contribute decisively to sustainability through carbon dioxide fixation and minimization of agricultural land use. This paper reviews current knowledge of the effects of consuming edible microalgae on the metabolic alterations known as metabolic syndrome (MS). These microalgae include Chlorella, Spirulina (Arthrospira) and Tetraselmis as well as Isochrysis and Nannochloropsis as candidates for human consumption. Chlorella biomass has shown antioxidant, antidiabetic, immunomodulatory, antihypertensive, and antihyperlipidemic effects in humans and other mammals. The components of microalgae reviewed suggest that they may be effective against MS at two levels: in the early stages, to work against the development of insulin resistance (IR), and later, when pancreatic -cell function is already compromised. The active components at both stages are antioxidant scavengers and anti-inflammatory lipid mediators such as carotenoids and -3 PUFAs (eicosapentaenoic acid/docosahexaenoic acid; EPA/DHA), prebiotic polysaccharides, phenolics, antihypertensive peptides, several pigments such as phycobilins and phycocyanin, and some vitamins, such as folate. As a source of high-quality protein, including an array of bioactive molecules with potential activity against the modern epidemics of obesity and diabetes, microalgae are proposed as excellent foods for the future. Moreover, their incorporation into the human diet would decisively contribute to a more sustainable world because of their roles in carbon dioxide fixation and reducing the use of land for agricultural purposes.


Assuntos
Fatores Biológicos/administração & dosagem , Doenças Metabólicas/prevenção & controle , Doenças Metabólicas/terapia , Microalgas , Animais , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Chlorella/química , Diabetes Mellitus , Dieta , Proteínas Alimentares/administração & dosagem , Alimento Funcional , Humanos , Hipoglicemiantes/administração & dosagem , Microalgas/química , Microalgas/fisiologia , Obesidade , Spirulina/química
9.
PLoS One ; 15(11): e0240686, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33142314

RESUMO

This study examines the influence of intermittent exposure to cold, hypobaric hypoxia, and their combination, in gut microbiota and their metabolites in vivo, and explores their effects on the physiology of the host. Sprague-Dawley rats were exposed to cold (4°C), hypobaric hypoxia (462 torr), or both simultaneously, 4 h/day for 21 days. Biometrical and hematological parameters were monitored. Gut bacterial subgroups were evaluated by qPCR and short-chain fatty acids were determined by gas chromatography in caecum and feces. Cold increased brown adipose tissue, Clostridiales subpopulation and the concentration of butyric and isovaleric acids in caecum. Hypobaric hypoxia increased hemoglobin, red and white cell counts and Enterobacteriales, and reduced body and adipose tissues weights and Lactobacilliales. Cold plus hypobaric hypoxia counteracted the hypoxia-induced weight loss as well as the increase in white blood cells, while reducing the Bacteroidetes:Firmicutes ratio and normalizing the populations of Enterobacteriales and Lactobacilliales. In conclusion, intermittent cold and hypobaric hypoxia exposures by themselves modified some of the main physiological variables in vivo, while their combination kept the rats nearer to their basal status. The reduction of the Bacteroidetes:Firmicutes ratio and balanced populations of Enterobacteriales and Lactobacilliales in the gut may contribute to this effect.


Assuntos
Tecido Adiposo Marrom/metabolismo , Bactérias/classificação , Ácidos Graxos Voláteis/análise , Hipóxia/metabolismo , Animais , Bactérias/genética , Bactérias/isolamento & purificação , Ceco/química , Cromatografia Gasosa , Temperatura Baixa , Fezes/química , Microbioma Gastrointestinal , Masculino , Filogenia , Ratos Sprague-Dawley
10.
Foods ; 9(9)2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32933009

RESUMO

Polyphenols are dietary bioactive compounds able to induce modifications in the gut microbiota profile, although more clinical studies are needed. With this aim, a randomized cross-over clinical trial was conducted, where 49 subjects at cardiometabolic risk (exhibiting at least two metabolic syndrome factors) were supplemented with a daily dose of 8 g of grape pomace (GP) for 6 weeks, with an equivalent control (CTL) period. The levels of total bacteria and Bacteroidetes, Firmicutes, Lactobacilliales, Bacteroides and Prevotella were estimated in fecal DNA by quantitative real-time PCR (qPCR), while fecal short-chain fatty acids (SCFAs) were assessed by gas chromatography. Several cardiometabolic markers were evaluated in blood samples. GP reduced insulin levels only in half of the participants (responders). GP supplementation did not cause significant modifications in the microbiota profile of the whole group, except for a tendency (p = 0.059) towards a decrease in the proportion of Lactobacilliales, while it increased the proportion of Bacteroides in non-responder subjects. The reduction of insulin levels in subjects at cardiometabolic risk upon GP supplementation appears not to be induced by changes in the major subgroups of gut microbiota. Further studies at the species level may help to elucidate the possible role of microbiota in GP-induced insulinemic status.

11.
Mar Drugs ; 18(6)2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32560216

RESUMO

Diacylglycerols (DAG) and ceramides have been suggested as early predictors of insulin resistance. This study was aimed to examine the combined effects of fish oil (FO) and grape seed extract (GSE) on hepatic endogenous antioxidants, DAG and ceramides in diet-induced early stages of insulin resistance. Thirty-five rats were fed one of the following diets: (1) a standard diet (STD group), (2) a high-fat high-sucrose diet (HFHS group), (3) an HFHS diet enriched with FO (FO group), (4) an HFHS diet enriched with GSE (GSE group) or (5) an HFHS diet enriched with FO and GSE (FO + GSE group). In the liver, endogenous antioxidants were measured using spectrophotometric and fluorometric techniques, and non-targeted lipidomics was conducted for the assessment of DAG and ceramides. After 24 weeks, the FO + GSE group showed increased glutathione peroxidase activity, as well as monounsaturated fatty acid and polyunsaturated fatty acid-containing DAG, and long-chain fatty acid-containing ceramides abundances compared to the STD group. The FO and GSE combination induced similar activation of the antioxidant system and bioactive lipid accumulation in the liver than the HFHS diet without supplementation. In addition, the FO and GSE combination increased the abundances of polyunsaturated fatty acid-containing DAG in the liver.


Assuntos
Antioxidantes/administração & dosagem , Suplementos Nutricionais , Óleos de Peixe/administração & dosagem , Extrato de Sementes de Uva/administração & dosagem , Resistência à Insulina , Fígado/efeitos dos fármacos , Animais , Ceramidas/análise , Ceramidas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Diglicerídeos/análise , Diglicerídeos/metabolismo , Modelos Animais de Doenças , Ácidos Graxos Insaturados , Feminino , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipidômica , Fígado/metabolismo , Ratos
12.
Nutrients ; 11(11)2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31683529

RESUMO

Some functional food components may help maintain homeostasis by promoting balanced gut microbiota. Here, we explore the possible complementary effects of d-fagomine and ω-3 polyunsaturated fatty acids (ω-3 PUFAs) eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA 1:1) on putatively beneficial gut bacterial strains. Male Sprague-Dawley rats were supplemented with d-fagomine, ω-3 PUFAs, or both, for 23 weeks. Bacterial subgroups were evaluated in fecal DNA by quantitative real-time polymerase chain reaction (qRT-PCR) and short-chain fatty acids were determined by gas chromatography. We found that the populations of the genus Prevotella remained stable over time in animals supplemented with d-fagomine, independently of ω-3 PUFA supplementation. Animals in these groups gained less weight than controls and rats given only ω-3 PUFAs. d-Fagomine supplementation together with ω-3 PUFAs maintained the relative populations of Bacteroides. ω-3 PUFAs alone or combined with d-fagomine reduced the amount of acetic acid and total short-chain fatty acids in feces. The plasma levels of pro-inflammatory arachidonic acid derived metabolites, triglycerides and cholesterol were lower in both groups supplemented with ω-3 PUFAs. The d-fagomine and ω-3 PUFAs combination provided the functional benefits of each supplement. Notably, it helped stabilize populations of Prevotella in the rat intestinal tract while reducing weight gain and providing the anti-inflammatory and cardiovascular benefits of ω-3 PUFAs.


Assuntos
Peso Corporal/efeitos dos fármacos , Ácidos Graxos Ômega-3/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Imino Piranoses/farmacologia , Administração Oral , Animais , Bacteroides/efeitos dos fármacos , Suplementos Nutricionais , Fagopyrum/química , Ácidos Graxos Ômega-3/administração & dosagem , Imino Piranoses/administração & dosagem , Masculino , Prevotella/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Alimentos Marinhos
13.
Sci Rep ; 9(1): 16628, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31719544

RESUMO

Food contains bioactive compounds that may prevent changes in gut microbiota associated with Westernized diets. The aim of this study is to explore the possible additive effects of D-fagomine and ω-3 PUFAs (EPA/DHA 1:1) on gut microbiota and related risk factors during early stages in the development of fat-induced pre-diabetes. Male Sprague Dawley (SD) rats were fed a standard diet, or a high-fat (HF) diet supplemented with D-fagomine, EPA/DHA 1:1, a combination of both, or neither, for 24 weeks. The variables measured were fasting glucose and glucose tolerance, plasma insulin, liver inflammation, fecal/cecal gut bacterial subgroups and short-chain fatty acids (SCFAs). The animals supplemented with D-fagomine alone and in combination with ω-3 PUFAs accumulated less fat than those in the non-supplemented HF group and those given only ω-3 PUFAs. The combined supplements attenuated the high-fat-induced incipient insulin resistance (IR), and liver inflammation, while increasing the cecal content, the Bacteroidetes:Firmicutes ratio and the populations of Bifidobacteriales. The functional effects of the combination of D-fagomine and EPA/DHA 1:1 against gut dysbiosis and the very early metabolic alterations induced by a high-fat diet are mainly those of D-fagomine complemented by the anti-inflammatory action of ω-3 PUFAs.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos Ômega-3/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Imino Piranoses/uso terapêutico , Estado Pré-Diabético/etiologia , Animais , Glicemia/análise , Quimioterapia Combinada , Ácidos Graxos Ômega-3/administração & dosagem , Teste de Tolerância a Glucose , Imino Piranoses/administração & dosagem , Insulina/sangue , Leptina/sangue , Masculino , Estado Pré-Diabético/microbiologia , Estado Pré-Diabético/prevenção & controle , Ratos , Ratos Sprague-Dawley , Fatores de Risco
14.
Mar Drugs ; 18(1)2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31906027

RESUMO

Diet-induced obesity has been linked to metabolic disorders such as cardiovascular diseases andtype 2 diabetes. A factor linking diet to metabolic disorders is oxidative stress, which can damagebiomolecules, especially proteins. The present study was designed to investigate the effect of marineomega-3 polyunsaturated fatty acids (PUFAs) (eicosapentaenoic acid (EPA) and docosahexaenoic acid(DHA)) and their combination with grape seed polyphenols (GSE) on carbonyl-modified proteins fromplasma and liver in Wistar Kyoto rats fed an obesogenic diet, namely high-fat and high-sucrose (HFHS)diet. A proteomics approach consisting of fluorescein 5-thiosemicarbazide (FTSC) labelling of proteincarbonyls, visualization of FTSC-labelled protein on 1-DE or 2-DE gels, and protein identification byMS/MS was used for the protein oxidation assessment. Results showed the efficiency of the combinationof both bioactive compounds in decreasing the total protein carbonylation induced by HFHS diet in bothplasma and liver. The analysis of carbonylated protein targets, also referred to as the 'carbonylome',revealed an individual response of liver proteins to supplements and a modulatory effect on specificmetabolic pathways and processes due to, at least in part, the control exerted by the supplements on theliver protein carbonylome. This investigation highlights the additive effect of dietary fish oils and grapeseed polyphenols in modulating in vivo oxidative damage of proteins induced by the consumption ofHFHS diets.


Assuntos
Ácidos Graxos Ômega-3/farmacologia , Fígado/efeitos dos fármacos , Polifenóis/farmacologia , Proteínas/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Sacarose Alimentar/efeitos adversos , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/farmacologia , Ácidos Graxos Ômega-3/administração & dosagem , Fígado/metabolismo , Obesidade/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/administração & dosagem , Carbonilação Proteica/efeitos dos fármacos , Proteômica , Ratos , Ratos Endogâmicos WKY , Vitis/química
15.
Mar Drugs ; 16(10)2018 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-30261666

RESUMO

The present study addressed the ability of long-chain ω-3 polyunsaturated fatty acids (ω-3 PUFA), i.e., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), to ameliorate liver protein damage derived from oxidative stress and induced by consumption of high-caloric diets, typical of Westernized countries. The experimental design included an animal model of Sprague-Dawley rats fed high-fat high-sucrose (HFHS) diet supplemented with ω-3 EPA and DHA for a complete hepatic proteome analysis to map carbonylated proteins involved in specific metabolic pathways. Results showed that the intake of marine ω-3 PUFA through diet significantly decreased liver protein carbonylation caused by long-term HFHS consumption and increased antioxidant system. Fish oil modulated the carbonylation level of more than twenty liver proteins involved in critical metabolic pathways, including lipid metabolism (e.g., albumin), carbohydrate metabolism (e.g., pyruvate carboxylase), detoxification process (e.g., aldehyde dehydrogenase 2), urea cycle (e.g., carbamoyl-phosphate synthase), cytoskeleton dynamics (e.g., actin), or response to oxidative stress (e.g., catalase) among others, which might be under the control of diet marine ω-3 PUFA. In parallel, fish oil significantly changed the liver fatty acid profile given by the HFHS diet, resulting in a more anti-inflammatory phenotype. In conclusion, the present study highlights the significance of marine ω-3 PUFA intake for the health of rats fed a Westernized diet by describing several key metabolic pathways which are protected in liver.


Assuntos
Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Doenças Metabólicas/dietoterapia , Estresse Oxidativo/efeitos dos fármacos , Carbonilação Proteica/efeitos dos fármacos , Animais , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Ácidos Graxos Ômega-3/farmacologia , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Ratos , Ratos Sprague-Dawley
16.
Am J Physiol Endocrinol Metab ; 314(6): E552-E563, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29351480

RESUMO

Insulin resistance (IR) and impaired glucose tolerance (IGT) are the first manifestations of diet-induced metabolic alterations leading to Type 2 diabetes, while hypertension is the deadliest risk factor of cardiovascular disease. The roles of dietary fat and fructose in the development of IR, IGT, and hypertension are controversial. We tested the long-term effects of an excess of fat or sucrose (fructose/glucose) on healthy male Wistar-Kyoto (WKY) rats. Fat affects IR and IGT earlier than fructose through low-grade systemic inflammation evidenced by liver inflammatory infiltration, increased levels of plasma IL-6, PGE2, and reduced levels of protective short-chain fatty acids without triggering hypertension. Increased populations of gut Enterobacteriales and Escherichia coli may contribute to systemic inflammation through the generation of lipopolysaccharides. Unlike fat, fructose induces increased levels of diacylglycerols (lipid mediators of IR) in the liver, urine F2-isoprostanes (markers of systemic oxidative stress), and uric acid, and triggers hypertension. Elevated populations of Enterobacteriales and E. coli were only detected in rats given an excess of fructose at the end of the study. Dietary fat and fructose trigger IR and IGT in clearly differentiated ways in WKY rats: early low-grade inflammation and late direct lipid toxicity, respectively; gut microbiota plays a role mainly in fat-induced IR, and hypertension is independent of inflammation-mediated IR. The results provide evidence that suggests that the combination of fat and sugar is potentially more harmful than fat or sugar alone when taken in excess.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Gorduras na Dieta/farmacologia , Açúcares da Dieta/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Hipertensão/etiologia , Resistência à Insulina , Animais , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Hipertensão/metabolismo , Hipertensão/patologia , Hipertensão/fisiopatologia , Masculino , Ratos , Ratos Endogâmicos WKY , Transdução de Sinais/efeitos dos fármacos , Aumento de Peso/efeitos dos fármacos
17.
Eur J Nutr ; 57(1): 339-349, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27730364

RESUMO

PURPOSE: Polyphenol metabolites are key mediators of the biological activities of polyphenols. This study aimed to evaluate the long-term effects of a high-fat high-sucrose (HFHS) diet on the metabolism of proanthocyanidins from grape seed extract (GSE). METHODS: Adult female Wistar-Kyoto rats were fed a standard (STD) or HFHS diet supplemented or not with GSE for 16 weeks. PA metabolites were determined by targeted HPLC-MS/MS analysis. RESULTS: A lower concentration of total microbial-derived PA metabolites was present in urine and the aqueous fraction of faeces in the HFHS + GSE group than in the STD + GSE group. In contrast, a tendency towards the formation of conjugated (epi)catechin metabolites in the HFHS + GSE group was observed. CONCLUSIONS: These results show that a HFHS diet significantly modifies PA metabolism, probably via: (1) a shift in microbial communities not counteracted by the polyphenols themselves; and (2) an up-regulation of hepatic enzymes.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Sacarose Alimentar/administração & dosagem , Extrato de Sementes de Uva/química , Proantocianidinas/metabolismo , Vitis , Animais , Catequina/metabolismo , Dieta , Fezes/química , Feminino , Microbioma Gastrointestinal/fisiologia , Extrato de Sementes de Uva/administração & dosagem , Proantocianidinas/administração & dosagem , Proantocianidinas/urina , Ratos , Ratos Endogâmicos WKY
18.
Food Res Int ; 97: 133-140, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28578033

RESUMO

Studies of the bioavailability of proanthocyanidins usually consider them independently of other dietary constituents, while there is a tendency in the field of functional foods towards the combination of different bioactive compounds in a single product. This study examined the long-term effects of ω-3 polyunsaturated fatty acids of marine origin on the metabolic fate of grape proanthocyanidins. For this, female adult Wistar-Kyoto rats were fed (18weeks) with a standard diet supplemented or not with eicosapentaenoic acid/docosahexaenoic acid (1:1, 16.6g/kg feed), proanthocyanidin-rich grape seed extract (0.8g/kg feed) or both. A total of 39 microbial-derived metabolites and 16 conjugated metabolites were detected by HPLC-MS/MS either in urine or in the aqueous fraction of feces. An unexpected significant increase in many proanthocyanidin metabolites in urine and feces was observed in the group supplemented with ω-3 polyunsaturated fatty acids group as compared to the animals fed a standard diet, which contains a small amount of polyphenols. However, proanthocyanidin metabolites in rats given ω-3 polyunsaturated fatty acids and grape seed extract did not significantly differ from those in the group supplemented only with grape seed extract. It was concluded that ω-3 polyunsaturated fatty acids collaborate in the metabolism of polyphenols when present at low doses in the feed matrix, while the capacity of ω-3 polyunsaturated fatty acids to induce microbiota transformations when proanthocyanidins are present at high doses is not relevant compared to that of polyphenols themselves.


Assuntos
Ácidos Graxos Ômega-3/metabolismo , Proantocianidinas/metabolismo , Animais , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Fezes/microbiologia , Feminino , Fermentação , Microbioma Gastrointestinal/fisiologia , Fenóis/metabolismo , Fenóis/urina , Ratos , Ratos Endogâmicos WKY , Espectrometria de Massas em Tandem
19.
Food Res Int ; 97: 364-371, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28578061

RESUMO

ω-3 Polyunsaturated fatty acids (PUFAs) reduce risk factors for cardiovascular diseases (CVD) and other pathologies that involve low-grade inflammation. They have recently been shown to exert complementary functional effects with proanthocyanidins. As the reduction of health-promoting gut bacteria such as lactobacilli and bifidobacteria has been linked to a number of alterations in the host, the aim of this study was to determine whether PUFAs and proanthocyanidins also cooperate in maintaining well-balanced microbiota. To this end, rats were supplemented for 6months with eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) 1:1 (16.6g/kg feed); proanthocyanidin-rich grape seed extract (GSE, 0.8g/kg feed); or both. Plasma adiponectin, cholesterol, and urine nitrites were measured. Gut bacterial subgroups were evaluated in fecal DNA by qRT-PCR. Short-chain fatty acids (SCFAs) were determined in feces by gas chromatography. Body and adipose tissue weights were found to be higher in the animals given ω-3 PUFAs, while their energy intake was lower. Plasma cholesterol was lower in ω-3 PUFA supplemented groups, while adiponectin and urine nitrites were higher. ω-3 PUFAs reduced the population of Lactobacillales and L. acidophilus after 6months of supplementation. GSE significantly reduced L. plantarum and B. longum. The combination of ω-3 PUFAs and GSE maintained the health-promoting bacteria at levels similar to those of the control group. Acetic acid was increased by the ω-3 PUFA individual supplementation, while the combination with GSE kept this value similar to the control value. In conclusion, while individual supplementations with ω-3 PUFAs or GSE modify the populations of Lactobacillus, Bifidobacterium and microbial products (SCFAs), their combination maintains the standard proportions of these bacterial subgroups and their function while also providing the cardiovascular benefits of ω-3 PUFAs.


Assuntos
Ácidos Graxos Ômega-3/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Proantocianidinas/farmacologia , Animais , Bactérias/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Fezes/microbiologia , Feminino , Lipídeos/sangue , Ratos , Ratos Wistar
20.
J Agric Food Chem ; 65(22): 4414-4420, 2017 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-28489364

RESUMO

d-Fagomine is an iminosugar found in buckwheat that is capable of inhibiting the adhesion of potentially pathogenic bacteria to epithelial mucosa and reducing the postprandial blood glucose concentration. This paper evaluates the excretion and metabolism of orally administered d-fagomine in rats and compares outcomes with the fate of 1-deoxynojirimycin. d-Fagomine and 1-deoxynojirimycin show similar absorption and excretion kinetics. d-Fagomine is partly absorbed (41-84%, dose of 2 mg/kg of body weight) and excreted in urine within 8 h, while the non-absorbed fraction is cleared in feces within 24 h. d-Fagomine is partially methylated (about 10% in urine and 3% in feces). The concentration of d-fagomine in urine from 1 to 6 h after administration is higher than 10 mg/L, the concentration that inhibits adhesion of Escherichia coli. Orally administered d-fagomine is partially absorbed and then rapidly excreted in urine, where it reaches a concentration that may be protective against urinary tract infections.


Assuntos
Fagopyrum/química , Imino Piranoses/farmacocinética , Extratos Vegetais/farmacocinética , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Imino Piranoses/administração & dosagem , Imino Piranoses/urina , Masculino , Espectrometria de Massas , Extratos Vegetais/administração & dosagem , Extratos Vegetais/urina , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
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