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1.
Int J Mol Sci ; 25(6)2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38542390

RESUMO

In arterial hypertension, the dysregulation of several metabolic pathways is closely associated with chronic immune imbalance and inflammation progression. With time, these disturbances lead to the development of progressive disease and end-organ involvement. However, the influence of cholecalciferol on metabolic pathways as a possible mechanism of its immunomodulatory activity in obesity-related hypertension is not known. In a phase 2, randomized, single-center, 24-week trial, we evaluated, as a secondary outcome, the serum metabolome of 36 age- and gender-matched adults with obesity-related hypertension and vitamin D deficiency, before and after supplementation with cholecalciferol therapy along with routine medication. The defined endpoint was the assessment of circulating metabolites using a nuclear magnetic resonance-based metabolomics approach. Univariate and multivariate analyses were used to evaluate the systemic metabolic alterations caused by cholecalciferol. In comparison with normotensive controls, hypertensive patients presented overall decreased expression of several amino acids (p < 0.05), including amino acids with ketogenic and glucogenic properties as well as aromatic amino acids. Following cholecalciferol supplementation, increases were observed in glutamine (p < 0.001) and histidine levels (p < 0.05), with several other amino acids remaining unaffected. Glucose (p < 0.05) and acetate (p < 0.05) decreased after 24 weeks in the group taking the supplement, and changes in the saturation of fatty acids (p < 0.05) were also observed, suggesting a role of liposoluble vitamin D in lipid metabolism. Long-term cholecalciferol supplementation in chronically obese and overweight hypertensives induced changes in the blood serum metabolome, which reflected systemic metabolism and may have fostered a new microenvironment for cell proliferation and biology. Of note, the increased availability of glutamine may be relevant for the proliferation of different T-cell subsets.


Assuntos
Hipertensão , Deficiência de Vitamina D , Adulto , Humanos , Colecalciferol/farmacologia , Colecalciferol/uso terapêutico , Glutamina/uso terapêutico , Glucose/uso terapêutico , Vitamina D/uso terapêutico , Obesidade/complicações , Obesidade/tratamento farmacológico , Suplementos Nutricionais , Deficiência de Vitamina D/complicações , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Aminoácidos/metabolismo , Método Duplo-Cego
2.
Vaccines (Basel) ; 11(3)2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36992076

RESUMO

The human microbiota comprises a group of microorganisms co-existing in the human body. Unbalanced microbiota homeostasis may impact metabolic and immune system regulation, shrinking the edge between health and disease. Recently, the microbiota has been considered a prominent extrinsic/intrinsic element of cancer development and a promising milestone in the modulation of conventional cancer treatments. Particularly, the oral cavity represents a yin-and-yang target site for microorganisms that can promote human health or contribute to oral cancer development, such as Fusobacterium nucleatum. Moreover, Helicobacter pylori has also been implicated in esophageal and stomach cancers, and decreased butyrate-producing bacteria, such as Lachnospiraceae spp. and Ruminococcaceae, have demonstrated a protective role in the development of colorectal cancer. Interestingly, prebiotics, e.g., polyphenols, probiotics (Faecalibacterium, Bifidobacterium, Lactobacillus, and Burkholderia), postbiotics (inosine, butyrate, and propionate), and innovative nanomedicines can modulate antitumor immunity, circumventing resistance to conventional treatments and could complement existing therapies. Therefore, this manuscript delivers a holistic perspective on the interaction between human microbiota and cancer development and treatment, particularly in aerodigestive and digestive cancers, focusing on applying prebiotics, probiotics, and nanomedicines to overcome some challenges in treating cancer.

3.
Nutrients ; 13(12)2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34959746

RESUMO

The paramount importance of a healthy diet in the prevention of type 2 diabetes is now well recognized. Blueberries (BBs) have been described as attractive functional fruits for this purpose. This study aimed to elucidate the cellular and molecular mechanisms pertaining to the protective impact of blueberry juice (BJ) on prediabetes. Using a hypercaloric diet-induced prediabetic rat model, we evaluated the effects of BJ on glucose, insulin, and lipid profiles; gut microbiota composition; intestinal barrier integrity; and metabolic endotoxemia, as well as on hepatic metabolic surrogates, including several related to mitochondria bioenergetics. BJ supplementation for 14 weeks counteracted diet-evoked metabolic deregulation, improving glucose tolerance, insulin sensitivity, and hypertriglyceridemia, along with systemic and hepatic antioxidant properties, without a significant impact on the gut microbiota composition and related mechanisms. In addition, BJ treatment effectively alleviated hepatic steatosis and mitochondrial dysfunction observed in the prediabetic animals, as suggested by the amelioration of bioenergetics parameters and key targets of inflammation, insulin signaling, ketogenesis, and fatty acids oxidation. In conclusion, the beneficial metabolic impact of BJ in prediabetes may be mainly explained by the rescue of hepatic mitochondrial bioenergetics. These findings pave the way to support the use of BJ in prediabetes to prevent diabetes and its complications.


Assuntos
Mirtilos Azuis (Planta) , Diabetes Mellitus Tipo 2/metabolismo , Ingestão de Energia/efeitos dos fármacos , Sucos de Frutas e Vegetais , Estado Pré-Diabético/metabolismo , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/prevenção & controle , Modelos Animais de Doenças , Metabolismo Energético/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Insulina/sangue , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Fígado/metabolismo , Mitocôndrias/metabolismo , Ratos
4.
Methods Mol Biol ; 1782: 229-247, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29851003

RESUMO

Metabolic reprogramming has been associated to a plethora of diseases, and there has been increased demand for methodologies able to determine the metabolic alterations that characterize the pathological states and help developing metabolically centered therapies. In this chapter, methodologies for monitoring TCA cycle turnover and its interaction with pyruvate cycling and anaplerotic reactions will be presented. These methodologies are based in the application of stable 13C isotope "tracers"/substrates and 13C-NMR isotopomer analysis of metabolic intermediates. These methodologies can be applied at several organizational levels, ranging from isolated organelles and organs to whole organisms/humans. For the sake of simplicity, only very simple and well-defined models will be presented, including isolated heart mitochondria and isolated perfused hearts and livers.


Assuntos
Isótopos de Carbono/análise , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13/métodos , Metabolismo Energético , Mitocôndrias Cardíacas/metabolismo , Perfusão/métodos , Animais , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13/instrumentação , Coração , Isomerismo , Fígado , Camundongos , Perfusão/instrumentação , Espectroscopia de Prótons por Ressonância Magnética/instrumentação , Espectroscopia de Prótons por Ressonância Magnética/métodos , Ratos
5.
CNS Neurosci Ther ; 23(2): 119-126, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27762079

RESUMO

INTRODUCTION: We recently showed that a single high dose of methamphetamine (METH) induces a persistent frontal cortical monoamine depletion that is accompanied by helpless-like behavior in mice. However, brain metabolic alterations underlying both neurochemical and mood alterations remain unknown. AIMS: Herein, we aimed at characterizing frontal cortical metabolic alterations associated with early negative mood behavior triggered by METH. Adult C57BL/6 mice were injected with METH (30 mg/kg, i.p.), and their frontal cortical metabolic status was characterized after probing their mood and anxiety-related phenotypes 3 days postinjection. RESULTS: Methamphetamine induced depressive-like behavior, as indicated by the decreased grooming time in the splash test and by a transient decrease in sucrose preference. At this time, METH did not alter anxiety-like behavior or motor functions. Depolarization-induced glucose uptake was reduced in frontocortical slices from METH-treated mice compared to controls. Consistently, astrocytic glucose transporter (GluT1) density was lower in the METH group. A proton high rotation magic angle spinning (HRMAS) spectroscopic approach revealed that METH induced a significant decrease in N-acetyl aspartate (NAA) and glutamate levels, suggesting that METH decreased neuronal glutamatergic function in frontal cortex. CONCLUSIONS: We report, for the first time, that a single METH injection triggers early self-care and hedonic deficits and impairs frontal cortical energetics in mice.


Assuntos
Anedonia/efeitos dos fármacos , Lesões Encefálicas/induzido quimicamente , Lesões Encefálicas/patologia , Estimulantes do Sistema Nervoso Central/toxicidade , Córtex Cerebral/efeitos dos fármacos , Metanfetamina/toxicidade , Animais , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Córtex Cerebral/patologia , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Preferências Alimentares/efeitos dos fármacos , Glucose/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Transportador de Glucose Tipo 3/metabolismo , Ácido Glutâmico/metabolismo , Asseio Animal/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos
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