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1.
Nutrients ; 12(4)2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32252241

RESUMO

Sphingolipid metabolism plays a critical role in cell growth regulation, lipid regulation, neurodevelopment, type 2 diabetes, and cancer. Animal experiments suggest that vitamin D may be involved in sphingolipid metabolism regulation. In this study, we tested the hypothesis that vitamin D supplementation would alter circulating long-chain ceramides and related metabolites involved in sphingolipid metabolism in humans. We carried out a post-hoc analysis of a previously conducted randomized, placebo-controlled clinical trial in 70 overweight/obese African-Americans, who were randomly assigned into four groups of 600, 2000, 4000 IU/day of vitamin D3 supplements or placebo for 16 weeks. The metabolites were measured in 64 subjects (aged 26.0 ± 9.4 years, 17% male). Serum levels of N-stearoyl-sphingosine (d18:1/18:0) (C18Cer) and stearoyl sphingomyelin (d18:1/18:0) (C18SM) were significantly increased after vitamin D3 supplementation (ps < 0.05) in a dose-response fashion. The effects of 600, 2000, and 4000 IU/day vitamin D3 supplementation on C18Cer were 0.44 (p = 0.049), 0.52 (p = 0.016), and 0.58 (p = 0.008), respectively. The effects of three dosages on C18SM were 0.30 (p = 0.222), 0.61 (p = 0.009), and 0.68 (p = 0.004), respectively. This was accompanied by the significant correlations between serum 25-hydroxyvitamin D3 [25(OH)D] concentration and those two metabolites (ps < 0.05). Vitamin D3 supplementations increase serum levels of C18Cer and C18SM in a dose-response fashion among overweight/obese African Americans.


Assuntos
Afro-Americanos , Calcifediol/sangue , Colecalciferol/administração & dosagem , Glicoesfingolipídeos Neutros/metabolismo , Obesidade/metabolismo , Adulto , Afro-Americanos/etnologia , Colecalciferol/metabolismo , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Obesidade/etnologia , Sobrepeso/etnologia , Sobrepeso/metabolismo
2.
Poult Sci ; 99(4): 2041-2047, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32241489

RESUMO

The influence of dietary vitamin D3 (VD3) levels on growth, bone performance, and duodenal type IIb sodium-dependent phosphate cotransporter (NaPi-IIb) genes in broiler chicken were studied. One-day-old male Ross308 broilers (n = 432) were allocated into 6 treatment groups with each group consisting of 6 cage pens. Each treatment group received diet containing different amounts of VD3 (80, 200, 500, 1,250, 3,125, or 7,813 IU per kg of diet) from a day-old to 31 D of age. Dietary available phosphorus and calcium were kept the same across all treatments in each phase. At 14 D, influence of VD3 on BW gain was found in the birds that received VD3 of 3,125 IU/kg and 200 IU/kg (P < 0.05). Toe ash and tibia ash linearly increased (P < 0.05) at 14 D with increase in dietary VD3. There was no significant influence of dietary VD3 on tibia breaking strength. In both phases, relative expression of duodenal NaPi-IIb linearly increased (P < 0.01) with increase in dietary VD3. At 14 D, highest expression of 3.2 folds was observed in birds treated with VD3 at 7,813 IU/kg of feed. At 31 D, birds that received VD3 levels of 3,125 and 7,813 IU/kg of feed showed 2.9 folds higher in NaPi-IIb expression compared with those fed lowest level of VD3 at 80 IU/kg of feed. When dietary calcium and phosphorus were maintained at the standard requirement, increase in dietary VD3 did not improve growth performance. For optimum growth and bone characteristics, dietary inclusion of VD3 at 500 IU/kg was adequate for both starter and grower broiler diets. Vitamin D3 enhanced the expression of NaPi-IIb at higher doses and thus improving the tibia ash content in high VD3 treatment groups. This study reported for the first time an increased in the expression of duodenal NaPi-IIb in 31-day-old broilers in response to high dietary VD3 levels.


Assuntos
Proteínas Aviárias/metabolismo , Osso e Ossos/química , Galinhas/metabolismo , Colecalciferol/metabolismo , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIb/metabolismo , Ração Animal/análise , Animais , Proteínas Aviárias/genética , Galinhas/crescimento & desenvolvimento , Colecalciferol/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Masculino , Distribuição Aleatória , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIb/genética
3.
Am J Respir Crit Care Med ; 202(3): 371-382, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32186892

RESUMO

Rationale: Vitamin D deficiency is common in patients with asthma and chronic obstructive pulmonary disease (COPD). Low 25-hydroxyvitamin D (25[OH]D) levels may represent a cause or a consequence of these conditions.Objectives: To determine whether vitamin D metabolism is altered in asthma or COPD.Methods: We conducted a longitudinal study in 186 adults to determine whether the 25(OH)D response to six oral doses of 3 mg vitamin D3, administered over 1 year, differed between those with asthma or COPD versus control subjects. Serum concentrations of vitamin D3, 25(OH)D3, and 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3) were determined presupplementation and postsupplementation in 93 adults with asthma, COPD, or neither condition, and metabolite-to-parent compound molar ratios were compared between groups to estimate hydroxylase activity. Additionally, we analyzed 14 datasets to compare expression of 1α,25(OH)2D3-inducible gene expression signatures in clinical samples taken from adults with asthma or COPD versus control subjects.Measurements and Main Results: The mean postsupplementation 25(OH)D increase in participants with asthma (20.9 nmol/L) and COPD (21.5 nmol/L) was lower than in control subjects (39.8 nmol/L; P = 0.001). Compared with control subjects, patients with asthma and COPD had lower molar ratios of 25(OH)D3-to-vitamin D3 and higher molar ratios of 1α,25(OH)2D3-to-25(OH)D3 both presupplementation and postsupplementation (P ≤ 0.005). Intergroup differences in 1α,25(OH)2D3-inducible gene expression signatures were modest and variable if statistically significant.Conclusions: Attenuation of the 25(OH)D response to vitamin D supplementation in asthma and COPD associated with reduced molar ratios of 25(OH)D3-to-vitamin D3 and increased molar ratios of 1α,25(OH)2D3-to-25(OH)D3 in serum, suggesting that vitamin D metabolism is dysregulated in these conditions.


Assuntos
Asma/metabolismo , Calcifediol/metabolismo , Calcitriol/metabolismo , Colecalciferol/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Vitaminas/metabolismo , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Estudos de Casos e Controles , Colecalciferol/farmacocinética , Colestanotriol 26-Mono-Oxigenase/genética , Citocromo P-450 CYP3A/genética , Família 2 do Citocromo P450/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Polimorfismo de Nucleotídeo Único , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteína de Ligação a Vitamina D/genética , Vitamina D3 24-Hidroxilase/genética , Vitaminas/farmacocinética
4.
Anticancer Res ; 40(2): 719-722, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32014913

RESUMO

AIM: A commercially available light emitting diode (LED) that transmitted narrow band ultraviolet B (UVB) radiation was evaluated for its efficacy and efficiency to produce vitamin D3 in human skin. MATERIALS AND METHODS: Human skin samples were obtained from surgical procedures. The LED had peak emission wavelength of 295 nm. Skin samples were exposed to the UVB-LED for varying times and then were analyzed by high-pressure liquid chromatography (HPLC) to determine the vitamin D3 content. RESULTS: There was a statistically significant time- and dose-dependent increase in the percent of 7-dehydrocholesterol that was converted to vitamin D3 in the skin type II samples; 1.3%±0.5, 2.3%±0.6 and 4.5%±1.67 after exposure to 0.75 (11.7 mJ/cm2), 1.5 (23.4 mJ/cm2) and 3 (46.8 mJ/cm2) minimal erythemal doses (MEDs), respectively. CONCLUSION: The UVB-LED was effective and efficient in generating vitamin D3 in human skin, in vitro. The amount of vitamin D3 production increased in a dose-dependent fashion with increased UVB energy. UVB-LEDs can be developed for devices that can efficiently produce vitamin D3 in human skin.


Assuntos
Colecalciferol/biossíntese , Pele/metabolismo , Pele/efeitos da radiação , Raios Ultravioleta , Colecalciferol/metabolismo , Cromatografia Líquida de Alta Pressão , Desidrocolesteróis/metabolismo , Relação Dose-Resposta à Radiação , Humanos
5.
Int Arch Allergy Immunol ; 181(1): 56-70, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31707382

RESUMO

INTRODUCTION: Phospholipases are enzymes that occur in many types of human cells, including mast cells, and play an important role in the molecular background of asthma pathogenesis, and the development of inflammation NF-κB activities that affect numerous biological processes has been reported in many inflammatory diseases including asthma. Vitamin D is a widely studied factor that affects many diseases, including asthma. The aim of this study is to assess the influence of 1,25-(OH)2D3 on regulation of chosen phospholipase-A2 (PLA2) expression-selected inflammation mediators. METHODS: LUVA mast cells were stimulated with 1,25(OH)2D3, and inhibitors of NF-κB p65 and ubiquitination. Expression analysis of phospholipases (PLA2G5, PLA2G10, PLA2G12, PLA2G15, PLA2G4A, PLA2G4B, PLA2G4C, PLAA, NF-κB p65, and UBC) was done utilizing real-time PCR and Western blot. Eicosanoid (LTC4, LXA4, 15[S]-HETE, and PGE2) levels and sPLA2 were also measured. RESULTS: We found that 1,25(OH)2D3 decreased the expression of PLA2G5, PLA2G15, PLA2G5,UBC, and NF-κB p65 but increased expression of PLAA and PLA2G4C (p < 0.05). Moreover, the expression of PLA2G5 and PLA2G15 decreased after inhibition of NF-κB p65 and UBC. Increased levels of released LXA4 and 15(S)-HETE, decreased levels of LTC4, and sPLA2s enzymatic activity in response to 1,25(OH)2D3 were also observed. Additionally, NF-κB p65 inhibition led to an increase in the LXA4 concentration. CONCLUSION: Future investigations will be needed to further clarify the role of 1,25(OH)2D3 in the context of asthma and the inflammatory process; however, these results confirm a variety of effects which can be caused by this vitamin. 1,25(OH)2D3-mediated action may result in the development of new therapeutic strategies for asthma treatment.


Assuntos
Asma/metabolismo , Colecalciferol/metabolismo , Inflamação/metabolismo , Mastócitos/metabolismo , NF-kappa B/metabolismo , Fosfolipases A2/metabolismo , Asma/genética , Linhagem Celular Transformada , Regulação da Expressão Gênica , Humanos , Inflamação/genética , Lipoxinas/metabolismo , NF-kappa B/genética , Fosfolipases A2/genética , Transdução de Sinais , Ubiquitinação
6.
Int J Biochem Cell Biol ; 119: 105665, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31821883

RESUMO

Vitamin D3 is among the major neurosteroids whose role in developing and adult brain is intensively studied now. Its active form 1,25(OH)2D3 regulates the expression and functioning of a range of brain-specific proteins, which orchestrate the neurotransmitter turnover, neurogenesis and neuroplasticity. Despite numerous studies of the vitamin D role in normal and pathological brain function, there is little evidence on the mechanisms of alterations in excitatory and inhibitory neurotransmission under vitamin D deficiency (VDD). Using the animal model we characterized the dysfunction of excitatory and inhibitory neurotransmission under alimentary VDD. The shift between unstimulated and evoked GABA release under VDD was largely reversed after treatment of VDD, whereas the impairments in glutamatergic system were only partially recovered after 1-month vitamin D3 supplementation. The increase of the external glutamate level and unstimulated GABA release in brain nerve terminals was associated with intensified ROS production and higher [Ca2+]i in presynapse. The negative allosteric modulation of presynaptic mGlu7 receptors significantly enhanced exocytotic GABA release, which was decreased under VDD, thereby suggesting the neuroprotective effect of such modulation of inhibitory neurotransmission. Synaptic plasma membranes and cytosolic proteins contribute to the decreased stimulated release of neurotransmitter, by being the crucial components, whose functional state is impaired under VDD. The critical changes with synaptic vesicles occurred at the docking step of the process, whereas malfunctioning of synaptic cytosolic proteins impacted the fusion event foremost. The decreased amplitude of exocytosis was inherent for non-excitable cells as well, as evidenced by lower platelet degranulation. Our data suggest the presynaptic dysfunction and proinflammatory shift as the early events in the pathogenesis of VDD-associated disorders and provide evidences for the neuroprotective role of vitamin D3.


Assuntos
Encéfalo/fisiopatologia , Colecalciferol/deficiência , Inflamação/fisiopatologia , Doenças do Sistema Nervoso/metabolismo , Sinapses/patologia , Deficiência de Vitamina D/fisiopatologia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Colecalciferol/metabolismo , Colecalciferol/farmacologia , Colesterol/metabolismo , Modelos Animais de Doenças , Ácido Glutâmico/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Masculino , Fusão de Membrana , Camundongos Endogâmicos C57BL , Doenças do Sistema Nervoso/fisiopatologia , Vias Neurais , Fosfolipídeos/metabolismo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Sinapses/metabolismo , Deficiência de Vitamina D/metabolismo , Vitaminas/farmacologia , Ácido gama-Aminobutírico/metabolismo
7.
Food Chem ; 303: 125416, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472385

RESUMO

Calcium and vitamin D3 were co-encapsulated in three types of water-in-oil-in-water (W/O/W) double emulsions stabilized with biopolymers: gum arabic, sodium alginate (Alg) and chitosan (Ch). Three calcium salts with different solubility were used: calcium carbonate (CaC), tricalcium phosphate (CaP) and calcium gluconate (CaG). In order to study the bioavailability of calcium and vitamin D3, the W/O/W double emulsions were subjected to digestion in simulated conditions using in vitro gastrointestinal models. The size of the oil droplets of all double emulsions increased in oral phase and decreased in gastric and intestinal phases. In the intestinal phase, the average diameter of oil globules in the W/O/W(Alg) and W/O/W(Ch) was d23 = 6.56 ±â€¯0.09 and d23 = 5.33 ±â€¯0.01 and the electro-kinetic potential was: ζ ≈ -25 mV and ζ ≈ -17 mV, respectively. Presence of calcium ions in the intestinal fluid decreased the free fatty acids content and decreased the bioaccessibility of vitamin D3 due to the inhibition of micellization process.


Assuntos
Cálcio/química , Colecalciferol/química , Disponibilidade Biológica , Cálcio/metabolismo , Colecalciferol/metabolismo , Digestão , Composição de Medicamentos , Emulsões/química , Trato Gastrointestinal/metabolismo , Humanos , Cinética , Modelos Biológicos , Solubilidade , Água/química
8.
Proc Natl Acad Sci U S A ; 116(45): 22552-22555, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31636184

RESUMO

Vitamin D and sunlight have each been reported to protect against the development of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). To date, the contribution of each has been unclear as ultra violet (UV) exposure also causes the generation of vitamin D in the skin. To examine whether the UV based suppression of EAE results, at least, in part from the production of vitamin D, we studied the effect of UV light on EAE in mice unable to produce 7-dehydroxycholesterol (7-DHC), the required precursor of vitamin D. Furthermore, we examined UV suppression of EAE in mice devoid of the vitamin D receptor (VDR). Our results demonstrate that UV light suppression of EAE occurs in the absence of vitamin D production and in the absence of VDR. Future investigations will focus on identifying the pathway responsible for the protective action of UV in EAE and presumably human MS.


Assuntos
Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/terapia , Esclerose Múltipla/terapia , Fototerapia , Receptores de Calcitriol/metabolismo , Vitamina D/metabolismo , Animais , Colecalciferol/análogos & derivados , Colecalciferol/metabolismo , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/genética , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/genética , Esclerose Múltipla/metabolismo , Receptores de Calcitriol/genética , Pele/metabolismo , Pele/efeitos da radiação , Raios Ultravioleta
9.
Nutr. hosp ; 36(5): 1205-1212, sept.-oct. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-184646

RESUMO

Introduction: much evidence confirms that vitamin D may be associated with an improvement in CD4 cell counts in HIV-infected individuals, where antiretroviral therapy (ART) is used and associated with decreased 25(OH)D levels. Objective: to carry out a systematic review on the effect of vitamin D supplementation on HIV-infected adult patients. Methods: the research was conducted in the databases Science Direct, PubMed, BVS, Scielo Cochrane and Periods, from February to April 2018, with publication limit from 2000 to 2018, without restriction of gender, ethnicity and involving individuals with age older than 18 years. To evaluate the quality of the studies, we used the protocol Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) and the Jadad scale. Results: the search initially resulted in 198 articles. After the selection process 5 articles were identified as eligible, where they highlight that vitamin D supplementation may be an associated and effective intervention to reduce hypovitaminosis. ART reduces vitamin D3 levels and changes its metabolism, being associated with the risk of mortality. However, adequate levels of 25(OH)D are positively associated with the number of CD4 + cells and the reduction of infection levels. Conclusion: vitamin D supplementation promotes immune recovery. However, the cases analysed were few, insufficient to fully confirm the benefits and recommend supplementation. Therefore, intervention studies are needed to elucidate the role of vitamin D in human protection against HIV infections


Introducción: muchas evidencias ratifican que la vitamina D puede estar asociada con la mejora de los niveles de células CD4 en individuos infectados por el VIH, tratados con terapia antirretroviral (ART) que se asocia a la disminución de los niveles de 25(OH)D. Objetivo: realizar una revisión sistemática sobre el efecto de la suplementación de vitamina D en pacientes adultos infectados con VIH. Métodos: la investigación fue realizada en las bases de datos Science Direct, PubMed, BVS, Scielo Cochrane y periódicos, de febrero a abril de 2018, con límite de publicación de 2000 a 2018, sin restricción de género, etnicidad y que involucra a individuos con edad mayores de 18 años. Para la evaluación de la calidad de los estudios, se utilizó el protocolo Preferred Reporting Items for Systematic Reviews y Meta-Analyzes (PRISMA) y la escala de Jadad. Resultados: la encuesta inicialmente resultó en 198 artículos. Después del proceso de selección, 5 artículos fueron identificados como elegibles, donde ponen de manifiesto que la suplementación con vitamina D puede ser una intervención asociada y eficaz para reducir la hipovitaminosis. La ART reduce niveles de la vitamina D3 y altera su metabolismo, estando asociada al riesgo de mortalidad. Sin embargo, los niveles adecuados de 25(OH)D están asociados positivamente al número de células CD4 + y la reducción de los niveles de infecciones. Conclusión: la suplementación de vitamina D promueve la recuperación inmunológica. Sin embargo, los casos analizados fueron pocos, insuficientes para confirmar totalmente los beneficios y recomendar la suplementación. Por lo tanto, estudios de intervención son necesarios para elucidar la actuación de la vitamina D en la protección humana contra las infecciones por el VIH


Assuntos
Humanos , Colecalciferol/administração & dosagem , Colecalciferol/metabolismo , Infecções por HIV/dietoterapia , Infecções por HIV/imunologia , Linfócitos T CD4-Positivos/imunologia , Reconstituição Imune
10.
Chemosphere ; 237: 124469, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31549635

RESUMO

High exposure to bisphenol A (BPA) in children has been associated with the outcomes of several diseases, including those related to developmental problems. To elucidate the mechanism of BPA mediated developmental toxicity, plasma and urine from rats exposed to BPA was analyzed with high resolution metabolomics, beginning from post-natal day 9, for 91 days. Female and male rats were orally administered 5 different BPA doses to elucidate dose- and sex-specific BPA effects. Regarding dose-specific effects, multivariate statistical analysis showed that metabolic shifts were considerably altered between 5, 50 and 250 mg BPA/kg bw/day in treated rats. A nonmonotonicity and monotonicity between BPA dose and metabolic response were major trajectories, showing overall metabolic changes in plasma and urine, respectively. Metabolic perturbation in the steroid hormone biosynthesis pathway was significantly associated with dose- and sex-specific BPA effects. Intermediate metabolites in the rate-limiting step of steroid hormone biosynthesis down-regulated steroid hormones in the 250 mg treatment. Further, our study identified that BPA increased urinary excretion of vitamin D3 and decreased its concentration in blood, suggesting that perturbation of vitamin D3 metabolism may be mechanistically associated with neurodevelopmental disorders caused by BPA. Three metabolites showed a decrease in sex difference with high BPA dose because female rats were more affected than males, which can be related with early puberty onset in female. In brief, the results demonstrated that BPA induces dose- and sex-specific metabolic shifts and that perturbation of metabolism can explain developmental problems.


Assuntos
Compostos Benzidrílicos/toxicidade , Colecalciferol/metabolismo , Disruptores Endócrinos/toxicidade , Fenóis/toxicidade , Esteroides/metabolismo , Animais , Criança , Feminino , Hormônios , Humanos , Metabolismo dos Lipídeos , Masculino , Metabolômica , Ratos , Caracteres Sexuais
11.
Fish Shellfish Immunol ; 94: 271-279, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31499202

RESUMO

Postoperative care is a critical step of pearl culture that ultimately determines culture success. To determine the effect of dietary vitamin D3 (VD3) levels on immunity and antioxidant capacity of pearl oyster Pinctada fucata martensii during postoperative care and explore the mechanisms behind this phenomenon, five isonitrogenous and isolipidic experimental diets were formulated by adding different levels of dietary VD3 (0, 500, 1000, 3000, and 10000 IU/kg), and the diets were fed to five experimental groups (EG1, EG2, EG3, EG4, and EG5) in turn and cultured indoors. The control group (CG) was cultured in the natural sea. Pearl oysters that were 1.5 years old were subjected to nucleus insertion. After culturing for 30 days, EG3 exhibited significantly higher survival rates than those in CG and EG5 (P < 0.05). Moreover, EG3 exhibited the highest activities of alkaline phosphatase, acid phosphatase, catalase, superoxide dismutase, and lysozyme. However, EG5 achieved the highest activities of glutathione peroxidase. Metabolomics-based profiling of pearl oysters fed with high levels of dietary VD3 (EG5) and optimum levels of dietary VD3 (EG3) revealed 76 significantly differential metabolites (SDMs) (VIP > 1 and P < 0.05). Pathway analysis indicated that SDMs were involved in 21 pathways. Furthermore, integrated key metabolic pathway analysis suggested that pearl oysters in EG5 regulated the pentose phosphate pathway, glutathione metabolism, sphingolipid metabolism, and arachidonic acid metabolism in response to stress generated from excessive VD3. These findings had significant implications on strengthening the future development and application of VD3 in aquaculture of pearl oyster P. f. martensii.


Assuntos
Antioxidantes/metabolismo , Colecalciferol/metabolismo , Imunidade Inata/efeitos dos fármacos , Metaboloma , Pinctada/efeitos dos fármacos , Animais , Aquicultura , Cromatografia Líquida , Relação Dose-Resposta a Droga , Espectrometria de Massas , Metabolômica , Pinctada/imunologia , Pinctada/metabolismo
12.
Nutrients ; 11(9)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443425

RESUMO

Vitamin D metabolism is actively modulated in adipose tissue during obesity. To better investigate this process, we develop a specific LC-HRMS/MS method that can simultaneously quantify three vitamin D metabolites, i.e., cholecalciferol, 25-hydroxyvitamin D3 (25(OH)D3), and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in a complex matrix, such as mouse adipose tissue and plasma. The method uses pretreatment with liquid-liquid or solid-phase extraction followed by derivatization using Amplifex® reagents to improve metabolite stability and ionization efficiency. Here, the method is optimized by co-eluting stable isotope-labelled internal standards to calibrate each analogue and to spike biological samples. Intra-day and inter-day relative standard deviations were 0.8-6.0% and 2.0-14.4%, respectively for the three derivatized metabolites. The limits of quantification (LoQ) achieved with Amplifex® derivatization were 0.02 ng/mL, 0.19 ng/mL, and 0.78 ng/mL for 1,25(OH)2D3, 25(OH)D3 and cholecalciferol, respectively. Now, for the first time, 1,25(OH)2D3 can be co-quantified with cholecalciferol and 25(OH)D3 in mouse adipose tissue. This validated method is successfully applied to study the impact of obesity on vitamin D status in mice.


Assuntos
Tecido Adiposo/metabolismo , Colecalciferol/metabolismo , Cromatografia Líquida , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Vitamina D/análogos & derivados , Animais , Dieta Hiperlipídica , Masculino , Camundongos Endogâmicos C57BL , Vitamina D/metabolismo
13.
J Diabetes Res ; 2019: 7894950, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281852

RESUMO

Objective: In diabetes mellitus, vitamin D3 deficiency affects sex hormone levels and male fertility; however, the mechanism leading to the disorder is unclear. This research was designed to investigate the mechanism of vitamin D3 deficiency and hypogonadism in diabetic rats. Our aim was to assess serum vitamin D3 levels and the relationship among vitamin D3, insulin-like growth factor-1 (IGF-1), and testicular function. Materials and Methods: Rats with streptozotocin-induced diabetes were randomly divided into four groups and treated with different doses of vitamin D3: no vitamin D3, low (0.025 µg/kg/day), high (0.1 µg/kg/day), and high (0.1 µg/kg/day) with JB-1 (the insulin-like growth factor-1 receptor inhibitor group, 100 µg/kg/day). The groups were compared with wild-type rats, which function as the control group. Various parameters such as vitamin D3 and IGF-1 were compared between the experimental and wild-type groups, and their correlations were determined. Results: Twelve weeks of vitamin D3 supplementation improved the testosterone levels, as shown by the increase in the level of serum IGF-1 in diabetic rats. Phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT), which was a downstream of the signaling pathway of IGF-1, was significantly increased after vitamin D3 treatment. Conclusions: The study shows that vitamin D3 may promote the expression of testosterone and improve testicular function in diabetic rats by activating PI3K/AKT via IGF-1.


Assuntos
Colecalciferol/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Testículo/fisiologia , Animais , Peso Corporal , Diabetes Mellitus Experimental/metabolismo , Hipogonadismo/metabolismo , Masculino , Tamanho do Órgão , Fosforilação , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
14.
Poult Sci ; 98(12): 6713-6720, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31265732

RESUMO

The objective of this experiment was to investigate the effects of various dietary concentrations of vitamin D3 (D3) on pullet and laying hen performance, eggshell quality, bone health, and yolk D3 content from day of hatch until 68 wk of age. Initially, 440 Hy-line W36-day-old chicks were randomly assigned to 5 dietary treatments: 1,681 (control); 8,348; 18,348; 35,014; 68,348 IU D3/kg. At 17 wk of age, pullets were assigned to experimental diets with 12 replicate groups of 6 birds. At 17 wk of age, pullets fed diets containing 8,348 and 35,014 IU D3/kg had an increased bone mineral density in comparison to the control fed birds (P ≤ 0.01). Body weights of pullets fed the diet with 68,348 IU D3/kg were lower than other treatments (P ≤ 0.01). Hen-housed egg production (HHEP) of hens fed the 35,014 IU D3/kg diet was increased in comparison to control-fed hens (P ≤ 0.01), whereas HHEP of those fed 68,348 IU D3/kg diet was reduced in comparison to all other treatments (P ≤ 0.01). Shell breaking strength of eggs from hens fed 8,348, 35,014 and 68,348 IU D3/kg was increased in comparison to eggs from control-fed birds (P ≤ 0.01). Fat-free tibia ash content of hens fed any of the diets supplemented with D3 (8,348 to 68,348 IU D3/kg) was increased in comparison to control-fed hens (P ≤ 0.05). Yolk D3 content increased linearly with dietary D3 and the D3 transfer efficiency for the control, 8,348 IU, 18,348 IU, 35,014 IU, and 68,348 IU D3 treatments were 8.24, 10.29, 11.27, 12.42, and 12.06%, respectively. These data suggest that supplementation of dietary D3 up to 35,014 IU D3/kg feed maintained if not increased laying hen performance and enhanced pullet and laying hen skeletal quality as well as yolk D3 content and eggshell quality. Feeding pullets at a higher level 68,348 IU of D3 resulted in reduced growth and ultimately decreased performance of laying hens.


Assuntos
Osso e Ossos/fisiologia , Galinhas/fisiologia , Colecalciferol/metabolismo , Casca de Ovo/fisiologia , Gema de Ovo/química , Vitaminas/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Osso e Ossos/efeitos dos fármacos , Galinhas/crescimento & desenvolvimento , Colecalciferol/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Casca de Ovo/efeitos dos fármacos , Gema de Ovo/efeitos dos fármacos , Feminino , Distribuição Aleatória , Reprodução/efeitos dos fármacos , Vitaminas/administração & dosagem
15.
Poult Sci ; 98(11): 5679-5690, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31222321

RESUMO

Coccidiosis penalizes calcium (Ca), phosphorus (P), and fat-soluble vitamin status, as well as bone mineralization in broiler chickens. We hypothesized that dietary vitamin D (VitD) supplementation in the form of 25-hydroxycholecalciferol (OHD), compared to cholecalciferol (D3), would improve bone mineralization in broilers receiving marginally deficient Ca/P diets, with more pronounced effects during malabsorptive coccidiosis. In a 2 VitD source × 2 Ca/P levels × 2 levels of infection factorial experiment (n = 6 pens per treatment, 6 birds/pen), Ross 308 broilers were assigned to an Aviagen-specified diet supplemented with 4,000 IU/kg of either OHD or D3 between days 11 and 24 of age. The diet contained adequate (A; 8.7:4.4 g/kg) or marginally deficient (M; 6.1:3.1 g/kg) total Ca and available (av)P levels. At day 12 of age, birds were inoculated with water (C) or 7,000 Eimeria maxima oocysts (I). Pen performance was measured over 12 days post-infection (pi). One bird per pen was assessed for parameters of bone mineralization and intestinal histomorphometric features (day 6 and 12 pi), as well as E. maxima replication and gross lesions of the small intestine (day 6 pi). There was no interaction between infection status and Ca/avP level on bone mineralization. Bone breaking strength (BS), ash weight (AW), and ash percentage (AP) were highest in broilers fed the OHD-supplemented A diets irrespective of infection status. Eimeria maxima infection impaired (P < 0.05) ADG and FCR pi; Ca and P status at day 6 pi; OHD status, BS, AW, and AP at day 12 pi; and intestinal morphology at day 6 and 12 pi. A- compared to M-fed broilers had higher BS, AW, and AP at day 6 pi, and AW at day 12 pi. VitD source affected only OHD status, being higher (P < 0.001) for OHD- than D3-fed broilers at day 6 and 12 pi. In conclusion, offering OHD and adequate levels of Ca and P improved bone mineralization, with no effect on performance. Dietary D3 and OHD supplemented at 4,000 IU/kg had similar effects on coccidiosis-infected and uninfected broilers, which led to the rejection of our hypothesis.


Assuntos
Cálcio/deficiência , Galinhas/fisiologia , Colecalciferol/metabolismo , Fósforo/deficiência , Vitaminas/metabolismo , Ração Animal/análise , Animais , Calcifediol/administração & dosagem , Calcifediol/metabolismo , Calcificação Fisiológica/efeitos dos fármacos , Cálcio na Dieta/análise , Galinhas/crescimento & desenvolvimento , Colecalciferol/administração & dosagem , Coccidiose/parasitologia , Coccidiose/veterinária , Dieta/veterinária , Suplementos Nutricionais/análise , Eimeria/fisiologia , Intestinos/efeitos dos fármacos , Intestinos/fisiologia , Fósforo na Dieta/análise , Doenças das Aves Domésticas/parasitologia , Vitaminas/administração & dosagem
16.
Carcinogenesis ; 40(8): 937-946, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31169292

RESUMO

Sporadic colon cancer accounts for approximately 80% of colorectal cancer (CRC) with high incidence in Western societies strongly linked to long-term dietary patterns. A unique mouse model for sporadic CRC results from feeding a purified rodent Western-style diet (NWD1) recapitulating intake for the mouse of common nutrient risk factors each at its level consumed in higher risk Western populations. This causes sporadic large and small intestinal tumors in wild-type mice at an incidence and frequency similar to that in humans. NWD1 perturbs intestinal cell maturation and Wnt signaling throughout villi and colonic crypts and decreases mouse Lgr5hi intestinal stem cell contribution to homeostasis and tumor development. Here we establish that NWD1 transcriptionally reprograms Lgr5hi cells, and that nutrients are interactive in reprogramming. Furthermore, the DNA mismatch repair pathway is elevated in Lgr5hi cells by lower vitamin D3 and/or calcium in NWD1, paralleled by reduced accumulation of relevant somatic mutations detected by single-cell exome sequencing. In compensation, NWD1 also reprograms Bmi1+ cells to function and persist as stem-like cells in mucosal homeostasis and tumor development. The data establish the key role of the nutrient environment in defining the contribution of two different stem cell populations to both mucosal homeostasis and tumorigenesis. This raises important questions regarding impact of variable human diets on which and how stem cell populations function in the human mucosa and give rise to tumors. Moreover, major differences reported in turnover of human and mouse crypt base stem cells may be linked to their very different nutrient exposures.


Assuntos
Carcinogênese/genética , Neoplasias do Colo/genética , Células-Tronco/metabolismo , Animais , Cálcio/metabolismo , Diferenciação Celular/genética , Proliferação de Células/genética , Colecalciferol/metabolismo , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Dieta Ocidental/efeitos adversos , Modelos Animais de Doenças , Homeostase/genética , Humanos , Mucosa Intestinal/metabolismo , Intestinos/crescimento & desenvolvimento , Camundongos , Avaliação Nutricional , Receptores Acoplados a Proteínas-G/genética , Transdução de Sinais/genética , Via de Sinalização Wnt/genética
17.
Clin Cardiol ; 42(8): 710-719, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31099039

RESUMO

BACKGROUND: Accumulating studies have suggested that gut microbiota (GM) dysbiosis and vitamin D3 deficiency each play an important role during the progression of hypertension (HTN). However, few studies have characterized the underlying interaction between GM shift and vitamin D3 deficiency in HTN patients. HYPOTHESIS: This study aimed to evaluate the possible crosstalk between GM dysbiosis and vitamin D deficiency in the pathogenesis of HTN. METHODS: In a cohort of 34 HTN patients and 15 healthy controls, we analyzed the fecal microbiota products, GM composition, and the interaction between GM and vitamin D3. RESULTS: Vitamin D3 was significantly decreased in feces of HTN patients (P = .006, vs controls) and was correlated with altered GM, including decreased Shannon index (R2 = 0.1296, P = .0111) and Pielou evenness (R2 = 0.1509, P = .0058). Moreover, vitamin D3 positively correlated with HTN-reduced bacterial genera, including Subdoligranulum (R2 = 0.181, P = .0023), Ruminiclostridium (R2 = 0.1217, P = .014), Intestinimonas (R2 = 0.2036, P = .0011), Pseudoflavonifractor (R2 = 0.1014, P = .0257), Paenibacillus (R2 = 0.089, P = .0373), and Marvinbryantia (R2 = 0.08173, P = .0464). Partial least squares structural equation modeling showed that 27.7% of the total effect of gut microbiome on HTN was mediated by limiting vitamin D production. Finally, receiver operating characteristic curve analysis revealed the predictive capacity of differential gut microbiome signatures and decreased vitamin D3 to distinguish HTN patients (AUC = 0.749, P = .006). CONCLUSIONS: Our findings suggest that the GM dysbiosis contributing to the development of HTN might be partially mediated by vitamin D3 deficiency. Future studies involving the underlying mechanism and intervention strategies targeting microbiome composition and vitamin D3 to counteract the progression of HTN are warranted.


Assuntos
Pressão Sanguínea/fisiologia , Colecalciferol/metabolismo , Disbiose/complicações , Microbioma Gastrointestinal/fisiologia , Hipertensão/etiologia , Deficiência de Vitamina D/complicações , Cromatografia Líquida , Progressão da Doença , Disbiose/metabolismo , Fezes/química , Fezes/microbiologia , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Deficiência de Vitamina D/metabolismo
18.
Oxid Med Cell Longev ; 2019: 2843121, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30944691

RESUMO

Brain ageing is a complex multifactorial process characterized by gradual and continuous loss of neuronal functions. It is hypothesized that at the basis of brain ageing as well as age-related diseases, there is an impairment of the antioxidant defense system leading to an increase of oxidative stress. In this study, two different biological aspects involved in brain ageing and neurodegeneration have been investigated: oxidative stress and iron accumulation damage. In primary mouse astrocytes, the stimulation with 50 µM lipoic acid (LA) and 100 nM vitamin D (vitD) was first investigated in a time-course study to determine the dosages to be used in combination and then in a permeability test using an in vitro blood-brain barrier. In a second set of experiments, the role of oxidative stress was investigated pretreating astrocytes with 200 µM H2O2 for 30 min. The ability of vitD and LA alone and combined together to prevent or repair the damage caused by oxidative stress was investigated after 24 h of stimulation by the MTT test, mitochondrial membrane potential measurement, and Western blot analysis. To induce neurodegeneration, cells were pretreated with 300 µM catalytic iron for 6 days and then treated with vitD and LA alone and combined for additional 6 days to investigate the protection exerted by combination, analyzing viability, ROS production, iron concentration, and activation of intracellular pathways. In our study, the combination of LA and vitD showed beneficial effects on viability of astrocytes, since the substances are able to cross the brain barrier. In addition, combined LA and vitD attenuated the H2O2-induced apoptosis through the mitochondrial-mediated pathway. The combination was also able to counteract the adverse conditions caused by iron, preventing its accumulation. All these data support the hypothesis of the synergistic and cooperative activity exerted by LA and vitD in astrocytes indicating a possible new strategy to slow down ageing.


Assuntos
Astrócitos/metabolismo , Colecalciferol/metabolismo , Ferro/metabolismo , Estresse Oxidativo/imunologia , Ácido Tióctico/metabolismo , Envelhecimento , Animais , Humanos , Camundongos
19.
BMC Res Notes ; 12(1): 216, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30961641

RESUMO

OBJECTIVE: Vitamin D receptor (VDR) activities have been noted for a number of B cell malignancies which showed varying sensitivities to vitamin D3 (1,25-dihydroxyvitamin D3, VD3, calcitriol) and its synthetic analogs. The objective of this study was to address the potential effects of VD3 and vitamin D3 analogs (VDAs) on the growth of Hodgkin's lymphoma (HL), a malignant pathology of B cell origin, in vitro. RESULTS: Immunofluorescence staining showed the expression of VDR by primary Hodgkin's (H) and Reed-Sternberg (RS)-HRS-tumor cells in HL histological sections. Western blot analyses revealed expression of VDR in the HL cell lines Hs445, HDLM2, KMH2, and L428. One-way analysis of variance (ANOVA) on data obtained from water-soluble tetrazolium 1 (WST-1) cell proliferation assay showed decreased cell growth in HDLM2 and L428, 72 h after treatment with 10 µM of either VD3 of VDAs. Western blot analyses showed that treatment of L428 cells with the VDAs (calcipotriol and EB1089) resulted in modest increases in nuclear accumulation of VDR (nuVDR) compared to either dimethyl sulfoxide (DMSO) or VD3 treatments. nuVDR for DMSO control and VD3 was comparable. These results suggest that VD3 or VDAs may affect growth of HL.


Assuntos
Calcitriol/análogos & derivados , Colecalciferol/farmacologia , Regulação Neoplásica da Expressão Gênica , Receptores de Calcitriol/genética , Vitamina D/análogos & derivados , Calcitriol/metabolismo , Calcitriol/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colecalciferol/metabolismo , Dimetil Sulfóxido/farmacologia , Doença de Hodgkin/metabolismo , Doença de Hodgkin/patologia , Humanos , Receptores de Calcitriol/agonistas , Receptores de Calcitriol/metabolismo , Vitamina D/metabolismo , Vitamina D/farmacologia
20.
J Physiol Biochem ; 75(2): 229-240, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30927227

RESUMO

Fibroblast growth factors (FGF) constitute a large family of proteins with pleiotropic effects on development, organogenesis, and metabolism. The FGF19 subclass includes growth factors circulating with the blood referred to as endocrine FGF. Representatives of the FGF19 subclass, including FGF19, FGF21, and FGF23, act via FGFR receptors. The proteins of FGF19 subfamily influence the enterohepatic circulation of bile, participate in glucose and lipid metabolism regulation, and maintenance of phosphorus and vitamin D3 homeostasis. FGF19 and FGF21 are activated under different physiological and pathological conditions.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Tecido Adiposo/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , Metabolismo dos Carboidratos , Colecalciferol/metabolismo , Diabetes Mellitus/metabolismo , Diabetes Mellitus/fisiopatologia , Glucuronidase/metabolismo , Humanos , Metabolismo dos Lipídeos , Obesidade/metabolismo , Obesidade/fisiopatologia , Fósforo/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Doenças Vasculares/metabolismo
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