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1.
Antioxidants (Basel) ; 13(2)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38397759

RESUMO

Obesity is a risk factor for highly prevalent age-related neurodegenerative diseases, the pathogenesis of whichinvolves mitochondrial dysfunction and protein oxidative damage. Lipoxidation, driven by high levels of peroxidizable unsaturated fatty acids and low antioxidant protection of the brain, stands out as a significant risk factor. To gain information on the relationship between obesity and brain molecular damage, in a porcine model of obesity we evaluated (1) the level of mitochondrial respiratory chain complexes, as the main source of free radical generation, by Western blot; (2) the fatty acid profile by gas chromatography; and (3) the oxidative modification of proteins by mass spectrometry. The results demonstrate a selectively higher amount of the lipoxidation-derived biomarker malondialdehyde-lysine (MDAL) (34% increase) in the frontal cortex, and positive correlations between MDAL and LDL levels and body weight. No changes were observed in brain fatty acid profile by the high-fat diet, and the increased lipid peroxidative modification was associated with increased levels of mitochondrial complex I (NDUFS3 and NDUFA9 subunits) and complex II (flavoprotein). Interestingly, introducing n3 fatty acids and a probiotic in the high-fat diet prevented the observed changes, suggesting that dietary components can modulate protein oxidative modification at the cerebral level and opening new possibilities in neurodegenerative diseases' prevention.

2.
Eur J Nutr ; 62(6): 2463-2473, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37148357

RESUMO

PURPOSE: Obesity during childhood has become a pandemic disease, mainly caused by a diet rich in sugars and fatty acids. Among other negative effects, these diets can induce cognitive impairment and reduce neuroplasticity. It is well known that omega-3 and probiotics have a beneficial impact on health and cognition, and we have hypothesized that a diet enriched with Bifidobacterium breve and omega-3 could potentiate neuroplasticity in prepubertal pigs on a high-fat diet. METHODS: Young female piglets were fed during 10 weeks with: standard diet (T1), high-fat (HF) diet (T2), HF diet including B. breve CECT8242 (T3) and HF diet including the probiotic and omega-3 fatty acids (T4). Using hippocampal sections, we analyzed by immunocytochemistry the levels of doublecortin (DCX) to study neurogenesis, and activity-regulated cytoskeleton-associated protein (Arc) as a synaptic plasticity related protein. RESULTS: No effect of T2 or T3 was observed, whereas T4 increased both DCX+ cells and Arc expression. Therefore, a diet enriched with supplements of B. breve and omega-3 increases neurogenesis and synaptic plasticity in prepubertal females on a HF diet from nine weeks of age to sexual maturity. Furthermore, the analysis of serum cholesterol and HDL indicate that neurogenesis was related to lipidic demand in piglets fed with control or HF diets, but the neurogenic effect induced by the T4 diet was exerted by mechanisms independent of this lipidic demand. CONCLUSION: Our results show that the T4 dietary treatment is effective in potentiating neural plasticity in the dorsal hippocampus of prepubertal females on a HF diet.


Assuntos
Bifidobacterium breve , Ácidos Graxos Ômega-3 , Animais , Feminino , Suínos , Ácidos Graxos Ômega-3/farmacologia , Hipocampo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Neurogênese
3.
Aging Dis ; 14(5): 1887-1916, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37196109

RESUMO

Non-targeted LC-MS/MS-based lipidomic analysis was conducted in post-mortem human grey matter frontal cortex area 8 (GM) and white matter of the frontal lobe centrum semi-ovale (WM) to identify lipidome fingerprints in middle-aged individuals with no neurofibrillary tangles and senile plaques, and cases at progressive stages of sporadic Alzheimer's disease (sAD). Complementary data were obtained using RT-qPCR and immunohistochemistry. The results showed that WM presents an adaptive lipid phenotype resistant to lipid peroxidation, characterized by a lower fatty acid unsaturation, peroxidizability index, and higher ether lipid content than the GM. Changes in the lipidomic profile are more marked in the WM than in GM in AD with disease progression. Four functional categories are associated with the different lipid classes affected in sAD: membrane structural composition, bioenergetics, antioxidant protection, and bioactive lipids, with deleterious consequences affecting both neurons and glial cells favoring disease progression.

4.
Aging Cell ; 22(6): e13821, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36951231

RESUMO

Aging biology entails a cell/tissue deregulated metabolism that affects all levels of biological organization. Therefore, the application of "omic" techniques that are closer to phenotype, such as metabolomics, to the study of the aging process should be a turning point in the definition of cellular processes involved. The main objective of the present study was to describe the changes in plasma metabolome associated with biological aging and the role of sex in the metabolic regulation during aging. A high-throughput untargeted metabolomic analysis was applied in plasma samples to detect hub metabolites and biomarkers of aging incorporating a sex/gender perspective. A cohort of 1030 healthy human adults (45.9% females, and 54.1% males) from 50 to 98 years of age was used. Results were validated using two independent cohorts (1: n = 146, 53% females, 30-100 years old; 2: n = 68, 70% females, 19-107 years old). Metabolites related to lipid and aromatic amino acid (AAA) metabolisms arose as the main metabolic pathways affected by age, with a high influence of sex. Globally, we describe changes in bioenergetic pathways that point to a decrease in mitochondrial ß-oxidation and an accumulation of unsaturated fatty acids and acylcarnitines that could be responsible for the increment of oxidative damage and inflammation characteristic of this physiological process. Furthermore, we describe for the first time the importance of gut-derived AAA catabolites in the aging process describing novel biomarkers that could contribute to better understand this physiological process but also age-related diseases.


Assuntos
Aminoácidos Aromáticos , Metaboloma , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Aminoácidos Aromáticos/metabolismo , Envelhecimento/metabolismo , Metabolômica/métodos , Biomarcadores/metabolismo
5.
Antioxidants (Basel) ; 12(2)2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36829852

RESUMO

One of the richest tissues in lipid content and diversity of the human body is the brain. The human brain is constitutively highly vulnerable to oxidative stress. This oxidative stress is a determinant in brain aging, as well as in the onset and progression of sporadic (late-onset) Alzheimer's disease (sAD). Glycerophospholipids are the main lipid category widely distributed in neural cell membranes, with a very significant presence for the ether lipid subclass. Ether lipids have played a key role in the evolution of the human brain compositional specificity and functionality. Ether lipids determine the neural membrane structural and functional properties, membrane trafficking, cell signaling and antioxidant defense mechanisms. Here, we explore the idea that ether lipids actively participate in the pathogenesis of sAD. Firstly, we evaluate the quantitative relevance of ether lipids in the human brain composition, as well as their role in the human brain evolution. Then, we analyze the implications of ether lipids in neural cell physiology, highlighting their inherent antioxidant properties. Finally, we discuss changes in ether lipid content associated with sAD and their physiopathological implications, and propose a mechanism that, as a vicious cycle, explains the potential significance of ether lipids in sAD.

6.
Antioxidants (Basel) ; 12(1)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36671039

RESUMO

It is assumed that the human brain is especially susceptible to oxidative stress, based on specific traits such as a higher rate of mitochondrial free radical production, a high content in peroxidizable fatty acids, and a low antioxidant defense. However, it is also evident that human neurons, although they are post-mitotic cells, survive throughout an entire lifetime. Therefore, to reduce or avoid the impact of oxidative stress on neuron functionality and survival, they must have evolved several adaptive mechanisms to cope with the deleterious effects of oxidative stress. Several of these antioxidant features are derived from lipid adaptations. At least six lipid adaptations against oxidative challenge in the healthy human brain can be discerned. In this work, we explore the idea that neurons and, by extension, the human brain is endowed with an important arsenal of non-pro-oxidant and antioxidant measures to preserve neuronal function, refuting part of the initial premise.

7.
Nutrients ; 14(3)2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35276884

RESUMO

This study aimed to determine how the microbiota profile might be predisposed to a better response in blood lipid profiles due to dietary fibre supplementation. A three-arm intervention study that included three different fibre types (mainly insoluble, soluble, and antioxidant fibre) supplemented (19.2 g/day) during 2 months in individuals with hypercholesterolemia was developed. Changes in faecal microbiota and blood lipid profile after fibre supplementation were determined. In all volunteers, regardless of fibre type, an increase in the abundance of Bifidobacterium was observed, and similarly, an inverse relationship between faecal propionic acid and blood LDL-cholesterol, LDL particle size, and LDL/HDL particle ratio (p-values 0.0067, 0.0002, and 0.0067, respectively) was observed. However, not all volunteers presented an improvement in lipid profile. The non-responders to fibre treatment showed a decrease in microbiota diversity (Shannon and Simpson diversity index p-values of 0.0110 and 0.0255, respectively) after the intervention; where the reduction in short-chain fatty acids (SCFAs) producing bacterial genera such as Clostridium XIVa and Ruminococcus after dietary fibre treatment was the main difference. It was concluded that the non-responsiveness to dietary fibre treatment might be mediated by the lack of ability to maintain a stable SCFA producing bacteria diversity and composition after extra fibre intake.


Assuntos
Microbioma Gastrointestinal , Hipercolesterolemia , Microbiota , Fibras na Dieta , Ácidos Graxos Voláteis , Microbioma Gastrointestinal/fisiologia , Humanos
8.
Geroscience ; 44(2): 763-783, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35149960

RESUMO

Fatty acids are key components in the structural diversity of lipids and play a strategic role in the functional properties of lipids which determine the integrity of neuronal and glial cell membranes, the generation of lipid signaling mediators, and the chemical reactivity of acyl chains. The present study analyzes using gas chromatography the fatty acid profiles of 13 regions of the human central nervous system in healthy individuals ranging from 40 to 80 years old. The outcomes suggest the existence of general traits in fatty acid composition such as an average chain length of 18 carbon atoms, high monounsaturated fatty acid content, and predominance in polyunsaturated fatty acids of those of series n-6 over series n-3 which are shared by all brain regions regardless of age. Our results also show a general sustained and relatively well-preserved lipid profile throughout the adult lifespan in most studied regions (olive, upper vermis, substantia nigra, thalamus, hippocampus, putamen, caudate, occipital cortex, parietal cortex, entorhinal cortex, and frontal cortex) with minor changes that are region-dependent. In contrast, of particular relevance is the involvement of the inferior temporal cortex and cingulate cortex. It is proposed that during normal human brain aging, the lipid profile is resistant to changes with age in most human brain regions to ensure cell survival and function, but some particular regions involved in specific memory domains are greatly affected.


Assuntos
Envelhecimento , Encéfalo , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Encéfalo/metabolismo , Ácidos Graxos , Ácidos Graxos Insaturados/metabolismo , Humanos , Longevidade
9.
Int J Mol Sci ; 22(22)2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34830402

RESUMO

Lipids are closely associated with brain structure and function. However, the potential changes in the lipidome induced by aging remain to be elucidated. In this study, we used chromatographic techniques and a mass spectrometry-based approach to evaluate age-associated changes in the lipidome of the frontal cortex and cerebellum obtained from adult male Wistar rats (8 months), aged male Wistar rats (26 months), and aged male Wistar rats submitted to a methionine restriction diet (MetR)-as an anti-aging intervention-for 8 weeks. The outcomes revealed that only small changes (about 10%) were observed in the lipidome profile in the cerebellum and frontal cortex during aging, and these changes differed, in some cases, between regions. Furthermore, a MetR diet partially reversed the effects of the aging process. Remarkably, the most affected lipid classes were ether-triacylglycerols, diacylglycerols, phosphatidylethanolamine N-methylated, plasmalogens, ceramides, and cholesterol esters. When the fatty acid profile was analyzed, we observed that the frontal cortex is highly preserved during aging and maintained under MetR, whereas in the cerebellum minor changes (increased monounsaturated and decreased polyunsaturated contents) were observed and not reversed by MetR. We conclude that the rat cerebellum and frontal cortex have efficient mechanisms to preserve the lipid profile of their cell membranes throughout their adult lifespan in order to maintain brain structure and function. A part of the small changes that take place during aging can be reversed with a MetR diet applied in old age.


Assuntos
Envelhecimento/genética , Lobo Frontal/metabolismo , Lipídeos/genética , Metionina/metabolismo , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Cerebelo/metabolismo , Cerebelo/patologia , Cromatografia , Lobo Frontal/patologia , Humanos , Lipidômica/normas , Espectrometria de Massas , Estresse Oxidativo/genética , Ratos , Espécies Reativas de Oxigênio/metabolismo
10.
Mol Nutr Food Res ; 65(23): e2000499, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34599622

RESUMO

SCOPE: Diets with low content in advanced glycation end products (AGEs) lead to beneficial properties in highly prevalent age-related diseases. To shed light on the mechanisms behind, the changes induced by a low AGE dietary intervention in the circulating metabolome are analyzed. METHODS AND RESULTS: To this end, 20 non-diabetic patients undergoing peritoneal dialysis are randomized to continue their usual diet or to one with a low content of AGEs for 1 month. Then, plasmatic metabolome and lipidomes are analyzed by liquid-chromatography coupled to mass spectrometry. The levels of defined AGE structures are also quantified by ELISA and by mass-spectrometry. The results show that the low AGE diet impinged significant changes in circulating metabolomes (166 molecules) and lipidomes (91 lipids). Metabolic targets of low-AGE intake include sphingolipid, ether-lipids, and glycerophospholipid metabolism. Further, it reproduces some of the plasma characteristics of healthy aging. CONCLUSION: The finding of common pathways induced by low-AGE diets with previous metabolic traits implicated in aging, insulin resistance, and obesity suggest the usefulness of the chosen approach and supports the potential extension of this study to other populations.


Assuntos
Produtos Finais de Glicação Avançada , Resistência à Insulina , Dieta , Humanos , Lipidômica , Metaboloma
11.
Placenta ; 109: 4-10, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33895685

RESUMO

INTRODUCTION: Fatty acids are essential nutrients for the fetus and are supplied by the mother through the placenta. Desaturase and elongase enzymes play an important role in modulating the fatty acid composition of body tissues. We aimed to compare the fatty acid profile and the estimated desaturase and elongase activities in the placenta of appropriate (AGA) versus small-for-gestational-age (SGA), and to determine their relationship with the offspring size at birth. METHODS: The placental fatty acid profile was analyzed by gas chromatography in 84 infants (45 AGA and 30 SGA) from a prenatal cohort study. The estimated desaturase and elongase activities were calculated from product-precursor fatty acid ratios. Results were associated with maternal (age, body mass index and weight gain during gestation) and neonatal (gestational age, sex, birth weight and birth length) parameters. RESULTS: Differences in placental fatty acid composition between AGA and SGA infants rather than correlations thereof with neonatal parameters were observed. Placentas from SGA infants contained lower levels of omega-3 (ALA, EPA, DPA, and DHA) and high omega-6/omega-3 ratios (AA/DHA and LA/ALA), as well as low elongase (Elovl5) and high desaturase (D9Dn7 and D5Dn6) activity as compared to AGA infants (all p < 0.0001). DISCUSSION: Placentas of AGA and SGA infants differed in fatty acids profile as well as in estimated desaturase and elongase activities. A striking feature of SGA placentas was the low availability of omega-3. Hence, omega-3 fatty acid status deserves further attention, as a potential target of prenatal interventions.


Assuntos
Ácidos Graxos/análise , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Placenta/química , Nascimento a Termo , Adulto , Peso ao Nascer/fisiologia , Estudos de Casos e Controles , Estudos de Coortes , Ácidos Graxos/metabolismo , Feminino , Idade Gestacional , Humanos , Recém-Nascido/crescimento & desenvolvimento , Recém-Nascido/metabolismo , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Recém-Nascido Pequeno para a Idade Gestacional/metabolismo , Masculino , Placenta/metabolismo , Gravidez , Nascimento a Termo/metabolismo , Aumento de Peso/fisiologia
12.
Antioxidants (Basel) ; 9(11)2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33203089

RESUMO

The nonenzymatic adduction of malondialdehyde (MDA) to the protein amino groups leads to the formation of malondialdehyde-lysine (MDALys). The degree of unsaturation of biological membranes and the intracellular oxidative conditions are the main factors that modulate MDALys formation. The low concentration of this modification in the different cellular components, found in a wide diversity of tissues and animal species, is indicative of the presence of a complex network of cellular protection mechanisms that avoid its cytotoxic effects. In this review, we will focus on the chemistry of this lipoxidation-derived protein modification, the specificity of MDALys formation in proteins, the methodology used for its detection and quantification, the MDA-lipoxidized proteome, the metabolism of MDA-modified proteins, and the detrimental effects of this protein modification. We also propose that MDALys is an indicator of the rate of aging based on findings which demonstrate that (i) MDALys accumulates in tissues with age, (ii) the lower the concentration of MDALys the greater the longevity of the animal species, and (iii) its concentration is attenuated by anti-aging nutritional and pharmacological interventions.

13.
Molecules ; 25(18)2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32971886

RESUMO

Lipids were determinants in the appearance and evolution of life. Recent studies disclose the existence of a link between lipids and animal longevity. Findings from both comparative studies and genetics and nutritional interventions in invertebrates, vertebrates, and exceptionally long-lived animal species-humans included-demonstrate that both the cell membrane fatty acid profile and lipidome are a species-specific optimized evolutionary adaptation and traits associated with longevity. All these emerging observations point to lipids as a key target to study the molecular mechanisms underlying differences in longevity and suggest the existence of a lipidome profile of long life.


Assuntos
Membrana Celular/metabolismo , Metabolismo dos Lipídeos , Longevidade , Animais , Humanos
14.
Nutrients ; 12(9)2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899660

RESUMO

Egg-yolk based supplements have demonstrated biological effects. We have developed a novel processed egg-yolk (PEY) complement, and we have tested whether it has inflammation modulatory properties. These were evaluated in a lipopolysaccharide (LPS)-challenge in 1-month male rats by in vivo circulating cytokine profiles measured by multiplexing techniques. Cell culture was used to explore ex vivo properties of derived serum samples. We explored growth factor composition, and mass-spectrometry metabolome and lipidome analyses of PEY to characterize it. PEY significantly prevented LPS-induced increase in IL-1 ß, TNF-α, and MCP-1. Further, serum from PEY-treated animals abrogated LPS-induced iNOS build-up of the Raw 264.7 macrophage-like cell line. Immunochemical analyses demonstrated increased concentrations of insulin-like growth factor 1 (IGF-1), connective tissue growth factor (CTGF), and platelet-derived growth factor (PDGF) in the extract. PEY vs. egg-yolk comparative metabolomic analyses showed significative differences in the concentrations of at least 140 molecules, and in 357 in the lipidomic analyses, demonstrating the complexity of PEY. Globally, PEY acts as an orally-bioavailable immunomodulatory extract that may be of interest in those conditions associated with disarranged inflammation, such as inflammaging.


Assuntos
Anti-Inflamatórios/farmacocinética , Citocinas/efeitos dos fármacos , Suplementos Nutricionais , Gema de Ovo/química , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Animais , Disponibilidade Biológica , Células Cultivadas , Manipulação de Alimentos , Lipidômica , Lipopolissacarídeos , Masculino , Espectrometria de Massas , Metaboloma/efeitos dos fármacos , Camundongos , Células RAW 264.7 , Ratos
15.
J Nutr Biochem ; 83: 108393, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32512501

RESUMO

As obesity incidence is alarmingly rising among young individuals, we aimed to characterize an experimental model of this situation, considering the similarity between human and porcine physiology. For this reason, we fed prepubertal (63 days old) Duroc breed females (n=21) either with a standard growth diet (3800 kcal/day) or one with a high-calorie content (5200 kcal/day) during 70 days. Computerized tomography, mass-spectrometry-based metabolomics and lipidomics, as well as peripheral blood mononuclear cell transcriptomics, were applied to define traits linked to high-calorie intake. Samples from a human cohort confirmed potential lipidomic markers. Compared to those fed a standard growth diet, pigs fed a high-calorie diet showed an increased weight gain (13%), much higher adiposity (53%), hypertriacylglyceridemia and hypercholesterolemia in parallel to insulin resistance. This diet induced marked changes in the circulating lipidome, particularly in phosphatidylethanolamine-type molecules. Also, circulating specific diacylglycerol and monoacylglycerol contents correlated with visceral fat and intrahepatic triacylglycerol concentrations. Specific lipids associated with obesity in swine (mainly belonging to glycerophospholipid, triacylglyceride and sterol classes) were also linked with obesity traits in the human cohort, reinforcing the usefulness of the chosen approach. Interestingly, no overt inflammation in plasma or adipose tissue was evident in this model. The presented model is useful as a preclinical surrogate of prepubertal obesity in order to ascertain the pathophysiology interactions between energy intake and obesity development.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Obesidade Infantil/etiologia , Puberdade/metabolismo , Adiposidade , Animais , Modelos Animais de Doenças , Ingestão de Alimentos , Feminino , Humanos , Leucócitos Mononucleares/metabolismo , Obesidade Infantil/metabolismo , Obesidade Infantil/fisiopatologia , Fenômica , Puberdade/genética , Triglicerídeos/sangue
16.
Int J Mol Sci ; 20(23)2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31771102

RESUMO

Prolonged caloric intake above energy needs disturbs the body's ability to store and manage the excess of energy intake, leading to the onset of chronic degenerative diseases. This study aimed to compare the effect of three foods, which contain demonstrated bioactive compounds in the treatment of obesity and as an adjuvant in obesity energy restriction treatments. In a mice obesity model induced through a high-fat diet; fish oil, soluble fibre, and soy were incorporated to evaluate its capacity to modulate metabolic factors in adipose tissue during a continued fat intake or weight reduction through a normocaloric diet. As a result, fish oil improved mitochondrial related, adipose tissue hormone expression, and oxidation products when high-fat diets are consumed; while soluble fibre improved glucose and inflammation pathways during high-fat diet intake. In weight reduction treatments few differential features, as a treatment adjuvant, were observed for fish oil and soy; while soluble fibre was able to improve the weight reduction effects induced by a normocaloric diet. As a conclusion, soluble fibre supplementation compared to an energy reduction program, was the only treatment able to induce a significant additional effect in the improvement of weight loss and adipose tissue metabolism.


Assuntos
Tecido Adiposo , Dieta Redutora , Mitocôndrias , Obesidade , Redução de Peso , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/farmacologia , Modelos Animais de Doenças , Ingestão de Energia/efeitos dos fármacos , Óleos de Peixe/farmacologia , Masculino , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Obesidade/induzido quimicamente , Obesidade/dietoterapia , Obesidade/metabolismo , Obesidade/patologia
17.
Front Neurosci ; 13: 938, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31551694

RESUMO

Literature suggests that oxidative stress (OS) may be involved in the pathogenesis of multiple sclerosis (MS), in which the immune system is known to play a key role. However, to date, the OS in peripheral lymphocytes and its contribution to the disease remain unknown. The aim of the present study was to explore the influence of OS in peripheral lymphocytes of MS patients. To that end, a cross-sectional, observational pilot study was conducted [n = 58: 34 MS and 24 healthy subjects (control group)]. We have measured superoxide production and protein mitochondrial complex levels in peripheral blood mononuclear cells (PBMCs) isolated from MS patients and control. Lactate levels and the antioxidant capacity were determined in plasma. We adjusted the comparisons between study groups by age, sex and cell count according to case. Results demonstrated that PBMCs, specifically T cells, from MS patients exhibited significantly increased superoxide anion production compared to control group (p = 0.027 and p = 0.041, respectively). Increased superoxide production in PBMCs was maintained after the adjustment (p = 0.044). Regarding mitochondrial proteins, we observe a significant decrease in the representative protein content of the mitochondrial respiratory chain complexes I-V in PBMCs of MS patients (p = 0.002, p = 0.037, p = 0.03, p = 0.044, and p = 0.051, respectively), which was maintained for complexes I, III, and V after the adjustment (p = 0.026; p = 0.033; p = 0.033, respectively). In MS patients, a trend toward increased plasma lactate concentration was detected [8.04 mg lactate/dL (5.25, 9.49) in the control group, 11.36 mg lactate/dL (5.41, 14.81) in MS patients] that was statistically significant after the adjustment (p = 0.013). This might be indicative of compromised mitochondrial function. Finally, antioxidant capacity was also decreased in plasma from MS patients, both before (p = 0.027) and after adjusting for sex and age (p = 0.006). Our findings demonstrate that PBMCs of MS patients show impaired mitochondrial redox status and deficient antioxidant capacity. These results demonstrate for the first time the existence of mitochondrial alterations in the cells immune cells of MS patients already at the peripheral level.

18.
J Ethnopharmacol ; 243: 112090, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31315027

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng is a widely used ingredient in several traditional Chinese medicine formulation, mainly as a prophylactic and restorative agent. Ginseng's Chinese traditional formulations have shown protective effects against atherosclerosis, suggesting that ginseng may be useful for the treatment of metabolic disorders. AIM OF THE STUDY: To evaluate whether the supplementation with Panax ginseng (PG) has an effect on blood lipid profile in humans. MATERIALS AND METHODS: A meta-analysis and a systematic review were conducted to evaluate the effects of PG on blood lipid profile. RESULTS: A total of 18 studies met the inclusion criteria, from which 10 studies were performed in volunteers with at least one component of metabolic syndrome, 3 in postmenopausal women, 2 in healthy volunteers and 3 with other types of inclusion criteria. The doses employed ranged from 0.2 to 20 g/day (median 3 g/day, 95% CI 1.7, 5.8), while the treatment time ranged from 2 to 12 weeks (median 8 weeks, 95% CI 6, 9). Few studies reported the composition of the PG extract employed. The main ginsenosides reported were Rb1 and Rg1 (content ranging from Rb1 0.023-6.44 mg/g and Rg1 0.028-3.21 mg/g). Significant modification in blood profile was described in 7 studies, in which 5 studies observed a reduction in total cholesterol, 4 in LDL-cholesterol, and 2 in triacylglycerides. The meta-analysis of 10 studies in volunteers with parameters related with metabolic syndrome describes that PG may induce a mean difference compared to a placebo of -2.30 (95% CI -3.79,-0.80) and -1.47 (95% CI -1.90,-1.05) mg/dL per g/day of PG in the levels of total and LDL-cholesterol, with no significant effects in HDL-cholesterol and triacylglycerides. CONCLUSIONS: PG extract may induce an improvement in blood lipid profile mainly by a reduction in total and LDL-cholesterol levels.


Assuntos
Lipídeos/sangue , Panax , Extratos Vegetais/uso terapêutico , Suplementos Nutricionais , Humanos , Fitoterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
19.
Obesity (Silver Spring) ; 27(7): 1133-1140, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31112015

RESUMO

OBJECTIVE: This study aimed to characterize the differences in protein oxidation biomarkers in adipose tissue (AT) as an indicator of AT metabolism and bariatric surgery weight-loss success. METHODS: A human model, in which sixty-five individuals with obesity underwent bariatric surgery, and a diet-induced obesity animal model, in which animals were treated for 2 months with normocaloric diets, were analyzed to determine the associations between AT protein oxidation and body weight loss. Protein oxidative biomarkers were determined by gas chromatography/mass spectrometry in AT from human volunteers before the surgery, as well as 2 months after a diet treatment in the animal model. RESULTS: The levels of carboxyethyl-lysine (CEL) and 2-succinocystein (2SC) in both visceral and subcutaneous AT before the surgery directly correlated with greater weight loss in both human and animal models. 2SC levels in subcutaneous AT greater than 4.7 × 106  µmol/mol lysine (95% CI: 3.4 × 106 to 6.0 × 106 ) may predict greater weight loss after bariatric surgery (receiver operating characteristic curve area = 0.8222; P = 0.0047). Additionally, it was observed that individuals with diabetes presented lower levels of CEL and 2SC in subcutaneous AT (P = 0.0266 and P = 0.0316, respectively) compared with individuals without diabetes. CONCLUSIONS: CEL and 2SC in AT are useful biomarkers of AT metabolism and predict the individual's ability to reduce body weight after bariatric surgery.


Assuntos
Tecido Adiposo/metabolismo , Cirurgia Bariátrica/métodos , Biomarcadores/metabolismo , Obesidade/terapia , Proteínas/metabolismo , Redução de Peso/fisiologia , Adulto , Idoso , Animais , Modelos Animais de Doenças , Feminino , Glicosilação , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Oxirredução , Adulto Jovem
20.
PLoS One ; 12(8): e0182762, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28793331

RESUMO

Soybean is recognized as rich source of bioactive compounds for the improvement of glucose homeostasis. However, the post-prandial mechanisms of action have not been extensively described. The aim of this study is to determine the changes in glucose homeostasis and related factors after acute intake of a soy beverage. Twenty-nine subjects (15 women and 14 men, with an average age of 19.5 ± 1.2) ingested 500 mL of water, glucose (20.5 g/500 mL) and soy beverage (20 g of carbohydrate) in three separate sessions. Capillary blood glucose was monitored every 15 min until 120 min post-prandial, and blood samples were collected at baseline and after 60 min for insulin, incretin, free amino acids, antioxidant capacity and inflammation marker analysis. The increase in capillary glucose after soy-beverage intake was negligible. This is explained in part by an increase in 83% in insulin levels than induced with glucose alone, which is mainly mediated by a low insulin degradation ratio (determined by c-peptide ratio), incretins and likely also by the modulation of the antioxidant environment. No associations were observed between the insulin levels and soy amino acid uptake. It could be concluded that the acute low glycaemic response of a soy beverage may involves a relationship between incretin and insulin secretion and insulin degradation.


Assuntos
Aminoácidos/sangue , Glicemia/metabolismo , Peptídeo C/sangue , Incretinas/sangue , Insulina/sangue , Período Pós-Prandial/fisiologia , Leite de Soja , Adolescente , Estudos Cross-Over , Feminino , Índice Glicêmico , Humanos , Masculino , Adulto Jovem
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