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1.
Cell Prolif ; 54(4): e12989, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33609051

RESUMO

OBJECTIVES: Our aim was to investigate the prevalence and predictive variables of sarcopenia. METHODS: We recruited participants from the Peking Union Medical College Hospital Multicenter Prospective Longitudinal Sarcopenia Study (PPLSS). Muscle mass was quantified using bioimpedance, and muscle function was quantified using grip strength and gait speed. Logistic regression revealed the relationships between sarcopenia and nutritional, lifestyle, disease, psychosocial and physical variables. RESULTS: The prevalence of sarcopenia and sarcopenic obesity was 9.2%-16.2% and 0.26%-9.1%, respectively. Old age, single status, undernourishment, higher income, smoking, low physical activity, poor appetite and low protein diets were significantly associated with sarcopenia. Multiple logistic regression analysis showed that age was a risk factor for all stages of sarcopenia, and participants above 80 years were greater than fivefold more susceptible to sarcopenia, while lower physical activity was an independent risk factor. The optimal cut-off value for age was 71 years, which departs from the commonly accepted cut-off of 60 years. Female participants were greater than twofold less susceptible to sarcopenia than male participants. The sterol derivative 25-hydroxyvitamin D was associated with fourfold lower odds of sarcopenia in male participants. Several protein intake variables were also correlated with sarcopenia. Based on these parameters, we defined a highly predictive index for sarcopenia. CONCLUSIONS: Our findings support a predictive index of sarcopenia, which agglomerates the complex influences that sterol metabolism and nutrition exert on male vs female participants.


Assuntos
Proteínas/metabolismo , Sarcopenia/patologia , Esteróis/metabolismo , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Calcifediol/metabolismo , China/epidemiologia , Exercício Físico , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Fatores de Risco , Sarcopenia/epidemiologia , Fatores Sexuais , Testosterona/análise
2.
Anal Chem ; 93(4): 2273-2280, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33443406

RESUMO

It is well known that cell can response to various chemical and mechanical stimuli. Therefore, flow pressure variation induced by sample loading and elution should be small enough to ignore the physical impact on cells when we use a Chip-SPE-MS system for cells. However, most existent Chip-SPE-MS systems ignored the pressure alternation because it is extremely difficult to develop a homogeneous-flow-pressure hyphenated module. Herein, we developed an interesting fluidic isolation-assisted homogeneous-flow-pressure Chip-SPE-MS system and demonstrated that it is adequate for online high-throughput determination and quantification of the 25-hydroxyvitamin D3 (25(OH)D3) biotransformation in different cells. Briefly, the homogeneous ambient flow pressure is achieved by fluidic isolation between the cell culture channel and the SPE column, and an automatic sampling probe could accomplish the sample loading and dispensing to fulfill online pretreatment of the sample. Through this new system, the expression levels of 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) can be determined in real time with a detection limit of 2.54 nM. In addition, the results revealed that 25(OH)D3 metabolic activity differed significantly between normal L-02 cells and cancerous HepG2 cells. Treatment of L-02 cells with a high dose of 25(OH)D3 was found to increase significant formation of 24,25(OH)2D3, but this change was not apparent in HepG2 cells. The presented system promises to be a versatile tool for online accurate molecule biotransformation investigation and drug screening processes.


Assuntos
Calcifediol/metabolismo , Técnicas de Cultura de Células/instrumentação , Dispositivos Lab-On-A-Chip , Espectrometria de Massas/métodos , Microextração em Fase Sólida/métodos , Animais , Biotransformação , Linhagem Celular , Citocromo P-450 CYP3A/química , Citocromo P-450 CYP3A/metabolismo , Humanos , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Vitamina D3 24-Hidroxilase/química , Vitamina D3 24-Hidroxilase/metabolismo
3.
Poult Sci ; 99(5): 2608-2615, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32359596

RESUMO

This study was conducted to determine the effects of 25-hydroxycholecalciferol (25-OH-D3) on performance, egg quality, tibia quality, and serum hormones concentration in laying hens reared under high stocking density. A total of 800 45-week-old Lohmann laying hens were randomly allotted into a 2 × 2 factorial design with 2 levels of dietary 25-OH-D3 levels (0 and 69 µg/kg) and 2 rates of stocking densities [506 (low density) and 338 (high density) cm2/hen]. Laying hens were monitored for 16 wk. High stocking density decreased laying rate, egg weight, and feed intake compared with low stocking density (P < 0.01) during 1 to 8 wk and 1 to 16 wk. Overall, high stocking density increased eggshell lightness value and decreased shell redness and yellowness value, strength, thickness, and relative weight compared with low stocking density (P < 0.05). Dietary supplementation with 25-OH-D3 reduced the value of the eggshell lightness and increased its yellowness and eggshells weight (P ≤ 0.05). The increase in eggshell thickness was more pronounced when 25-OH-D3 was supplemented to layers under high stocking density (interaction, P < 0.05). Layers under high stocking density had lower ash content and calcium content in the tibia than layers under low stocking density (P = 0.04); dietary 25-OH-D3 increased tibia strength compared with no addition (P = 0.05). Layers under high stocking density had higher serum concentrations of 25-OH-D3, corticosterone (CORT), lipopolysaccharide (LPS), and osteocalcin (OC; P < 0.05), lower content of parathyroid hormone (PTH) compared with layers under low stocking density (P < 0.01). Dietary 25-OH-D3 increased serum concentration of 25-OH-D3, carbonic anhydrase (CA), and calcitonin (CT) (P < 0.01) and reduced corticosterone, lipopolysaccharide and osteocalcin concentration (P ≤ 0.05). The increase effect in PTH was more pronounced when 25-OH-D3 was supplemented to layers under high stocking density (interaction, P = 0.05). Overall, the results gathered in this study indicate that high stocking density result in reducing production performance, shell color and quality, and tibia health, whereas dietary 25-OH-D3 was able to maintain tibia health and to mitigate the negative impact of high stocking density on productive performance.


Assuntos
Calcifediol/metabolismo , Galinhas/fisiologia , Óvulo/química , Tíbia/química , Ração Animal/análise , Animais , Calcifediol/administração & dosagem , Galinhas/crescimento & desenvolvimento , Dieta/veterinária , Suplementos Nutricionais/análise , Feminino , Densidade Demográfica , Distribuição Aleatória
4.
Sci Rep ; 10(1): 5677, 2020 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-32231239

RESUMO

Recent studies have suggested that vitamin D activities involve vitamin D receptor (VDR)-dependent and VDR-independent effects of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 25-hydroxyvitamin D3 (25(OH)D3) and ligand-independent effects of the VDR. Here, we describe a novel in vivo system using genetically modified rats deficient in the Cyp27b1 or Vdr genes. Type II rickets model rats with a mutant Vdr (R270L), which recognizes 1,25(OH)2D3 with an affinity equivalent to that for 25(OH)D3, were also generated. Although Cyp27b1-knockout (KO), Vdr-KO, and Vdr (R270L) rats each showed rickets symptoms, including abnormal bone formation, they were significantly different from each other. Administration of 25(OH)D3 reversed rickets symptoms in Cyp27b1-KO and Vdr (R270L) rats. Interestingly, 1,25(OH)2D3 was synthesized in Cyp27b1-KO rats, probably by Cyp27a1. In contrast, the effects of 25(OH)D3 on Vdr (R270L) rats strongly suggested a direct action of 25(OH)D3 via VDR-genomic pathways. These results convincingly suggest the usefulness of our in vivo system.


Assuntos
Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Vitamina D/metabolismo , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Animais , Calcifediol/genética , Calcifediol/metabolismo , Calcitriol/farmacologia , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar , Raquitismo/metabolismo , Vitamina D/análogos & derivados , Vitamina D/genética , Vitamina D3 24-Hidroxilase/genética
5.
Poult Sci ; 99(3): 1241-1253, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32111302

RESUMO

Genetic selection and intensive nutrition for increased growth rate in meat-type ducks has resulted in an imbalance between pectorales increment and sternal mass, which is detrimental to productivity and welfare. Reducing body weight and increasing sternal mass probably reverses these adverse effects. Therefore, 2 experiments (Expt.) were conducted to investigate the effects of 25-hydroxycholecalciferol (25-OH-D3), a vitamin D3 metabolites, on sternal mass. In Expt. 1, 512 1-day-old male ducks were randomly assigned to 4 low-nutrient density diets and received following treatments in a 2 × 2 factorial arrangement: (i) NRC or China Agricultural industry standards (NY/T) vitamin premixes and (ii) 0.069 mg/kg 25-HyD in feed or not. At 49 D of age, regardless of 25-OH-D3, NY/T vitamin regimen inhibited bone turnover and consequently increased sternal trabecular bone volume and mineral deposition compared with NRC vitamin premix. Supplementing 25-OH-D3 to NRC but not NY/T vitamin regimen significantly improved sternal microarchitecture and mineral content, which companied by decreased serum bone resorption markers concentration, as well as downregulation of the gene expressions of osteoclast differentiation and activity. In Expt. 2, 256 1-day-old male ducks were fed a standard nutrient density diet contained NRC vitamin premix with 0 or 0.069 mg/kg of 25-OH-D3. Results also showed that 25-OH-D3 treatment significantly improved sternal mineral accumulation and microarchitecture, along with decreasing osteoblast and osteoclast numbers in bone surface, declining serum bone turnover markers levels, and increasing serum Ca concentration. Collectively, these findings indicated that the dietary administration of 25-OH-D3 increased sternal mass in NRC vitamin diet by suppressing bone resorption in 49-day-old meat duck.


Assuntos
Conservadores da Densidade Óssea/metabolismo , Calcifediol/metabolismo , Patos/fisiologia , Esterno/fisiologia , Vitaminas/metabolismo , Ração Animal/análise , Animais , Conservadores da Densidade Óssea/administração & dosagem , Calcifediol/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Masculino , Tamanho do Órgão , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Distribuição Aleatória
6.
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
7.
J Steroid Biochem Mol Biol ; 199: 105609, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32006587

RESUMO

Vitamin D plays a role in bone and metabolic health in life long, however hypovitaminosis D is common in different settings. The aim of this study was to describe vitamin D status among adolescents from a large sunny country and analyze associated factors. This was a multicenter, cross-sectional, school-based study. A total of 1152 adolescents age 12-17 from four Brazilian cities, Rio de Janeiro, Fortaleza, Brasília, and Porto Alegre, were included. Anthropometric variables, diet, type of school, race and season of data collection were evaluated. Serum concentrations of 25-hydroxyvitamin D [25(OH)D] were measured and categorized into three levels: ≤ 20 ng/mL, 21-29 ng/mL and ≥ 30 ng/mL. Ordered logistic regression models were used to explore the factors associated with hypovitaminosis D. The prevalence of vitamin D levels below 20 ng/mL, between 21 and 29 ng/mL and above 30 ng/mL was 21 % (95 %CI: 19 %-24 %), 42 % (95 %CI: 39 %-46 %) and 37 % (95 %CI: 33 %-40 %), respectively. In the final adjusted model, hypovitaminosis D was positively associated with gender, center (latitudes), data collected in winter or spring, non-whites, and private school students. A higher proportional odds ratio (POR) for hypovitaminosis D was found among obese boys (POR = 2.2, 95 %CI: 1.1-4.5), but not girls. Adequate dietary intake of vitamin D was a protective factor (POR = 0.4, 95 %CI: 0.2-0.6) against hypovitaminosis D. In conclusion, there is a high prevalence of Brazilian adolescents at risk of hypovitaminosis D, independent of region. Due to their potential benefits, lifestyle changes should be stimulated, including healthier food choices and spending more time outdoors (with sun protection).


Assuntos
Deficiência de Vitamina D/metabolismo , Vitamina D/análogos & derivados , Vitamina D/metabolismo , Adolescente , Brasil/epidemiologia , Calcifediol/metabolismo , Calcifediol/uso terapêutico , Criança , Estudos Transversais , Dieta , Feminino , Humanos , Estilo de Vida , Masculino , Fatores de Risco , Estações do Ano , Caracteres Sexuais , Luz Solar , Vitamina D/uso terapêutico , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/patologia
8.
Appl Microbiol Biotechnol ; 104(2): 765-774, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31776608

RESUMO

25-hydroxyvitamin D3 has attracted considerable attention due to its great medical value and huge market demand in animal husbandry. Microbial production of 25-hydroxyvitamin D3 has been recognized as an alternative superior to traditional chemical synthesis. In this study, a Gram-positive bacteria zju 4-2 (CCTCC M 2019385) was isolated from the soil using vitamin D3 as the sole carbon source and was identified as Bacillus cereus according to its physiological characteristics and 16S rRNA analysis, which also showed a relatively high capacity for 25-hydroxyvitamin D3 production. Through systematic optimization of different catalytic conditions, the optimal solvent system of vitamin D3, vitamin D3 addition time and concentration, temperature, and pH were shown to be propylene glycol/ethanol (v/v = 9:1), early stationary phase, 2 g/L, 37 °C, and pH 7.2, respectively. With these optimal conditions, 796 mg/L of 25-hydroxyvitamin D3 was achieved after 48 h bioconversion with zju 4-2 at the shake flask level. Finally, up to 830 mg/L 25-hydroxyvitamin D3 with a yield of 41.5% was obtained in a 5 L fermentation tank. Our developed biotransformation process with this newly isolated strain provides a platform to produce 25-hydroxyvitamin D3 efficiently at industrialization scale.


Assuntos
Bacillus cereus/isolamento & purificação , Bacillus cereus/metabolismo , Calcifediol/metabolismo , Hormônios e Agentes Reguladores de Cálcio/metabolismo , Colecalciferol/metabolismo , Bacillus cereus/classificação , Bacillus cereus/genética , Biotransformação , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Fermentação , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Microbiologia do Solo , Temperatura
9.
Rapid Commun Mass Spectrom ; 34(7): e8648, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31715032

RESUMO

RATIONALE: 25-Hydroxylated vitamin D is the best marker for vitamin D (VD). Due to its low ionization efficiency, a Cookson-type reagent, 1,2,4-triazoline-3,5-dione (TAD), is used to improve the detection/quantification of VD metabolites by liquid chromatography/tandem mass spectrometry (LC/MS/MS). However, the high reactivity of TAD makes its solution stability low and inconvenient for practical use. We here describe the development of a novel caged Cookson-type reagent, and we assess its performances in the quantitative and differential detection of four VD metabolites in serum using LC/MS/MS. METHODS: Caged 4-(4'-dimethylaminophenyl)-1,2,4-triazoline-3,5-dione (DAPTAD) analogues were prepared from 4-(4'-dimethylaminophenyl)-1,2,4-triazolidine-3,5-dione. Their stability and reactivity were examined. The optimized caged DAPTAD (14-(4-(dimethylamino)phenyl)-9-phenyl-9,10-dihydro-9,10-[1,2]epitriazoloanthracene-13,15-dione, DAP-PA) was used for LC/MS/MS analyses of VD metabolites. RESULTS: The solution stability of DAP-PA in ethyl acetate dramatically improved compared with that of the non-caged one. We measured the thermal retro-Diels-Alder reaction enabling the release of DAPTAD and found that the derivatization reaction was temperature-dependent. We also determined the detection limit and the lower limit of quantifications for four VD metabolites with DAPTAD derivatization. CONCLUSIONS: DAP-PA was stable enough for mid- to long-term storage in solution. This advantage shall contribute to the detection and quantification of VD in clinical laboratories, and as such to the broader use of clinical mass spectrometry.


Assuntos
Compostos de Anilina/química , Espectrometria de Massas em Tandem/métodos , Triazóis/química , Vitamina D/sangue , Vitamina D/metabolismo , 25-Hidroxivitamina D 2/análise , 25-Hidroxivitamina D 2/sangue , 25-Hidroxivitamina D 2/metabolismo , Compostos de Anilina/síntese química , Calcifediol/análise , Calcifediol/sangue , Calcifediol/metabolismo , Cromatografia Líquida , Humanos , Indicadores e Reagentes , Limite de Detecção , Triazóis/síntese química , Vitamina D/análise
10.
J Steroid Biochem Mol Biol ; 197: 105536, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31734492

RESUMO

Vitamin D has emerged as a potentially important molecule in ophthalmology. To date, all ophthalmic data pertaining to vitamin D has been restricted primarily to tear and serum analysis in human patients. Considering the isolated nature of the eye, we sought to determine the presence of intraocular vitamin D in ocular disease. METHODS: 25-Hydroxyvitamin D3 (25(OH)D3) concentrations were measured in the eye and blood of 120 participants undergoing ophthalmic procedures. Ocular localization of the 1,25-dihydroxyvitamin D3-generating (CYP27B1) and deactivating (CYP24A1) hydroxylases was performed by immunohistochemistry. Gene expression of CYP27B1, CYP24A1 and VEGF-A was measured in eyes from patients with and without disease. RESULTS: 25(OH)D3 was quantified in 112 ocular samples. In 40 cataract patient samples, the average 25(OH)D3 concentration was 0.057 ng/mL, compared to 72 retinal disease patient samples, average of 0.502 ng/mL (p < 0.001). Intraocular 25(OH)D3 did not correlate with serum levels of 25(OH)D3. There was no difference between the level of 25(OH)D3 measured in the aqueous and vitreous humour. The vitamin D-specific CYPs 27B1 and 24A1, strongly localized to complementary regions of the ciliary body, retinal pigment epithelium and neural retina. Gene expression analysis confirmed retinal CYP27B1 correlated strongly with VEGF-A in eyes from diabetic patients (r = 0.92, p < 0.001). CONCLUSIONS: Our data confirms that vitamin D is present in the humours of the human eye and that local synthesis/degradation is possible via the ocular CYP27B1 and CYP24A1. This argues for a functional role for local vitamin D production and signaling in the eye and suggests that vitamin D may be an important intraocular mediator in disease pathogenesis.


Assuntos
Calcifediol/metabolismo , Oftalmopatias/metabolismo , Olho/metabolismo , Vitamina D/metabolismo , Vitaminas/metabolismo , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos Transversais , Oftalmopatias/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vitamina D3 24-Hidroxilase/metabolismo , Adulto Jovem
11.
J Steroid Biochem Mol Biol ; 194: 105435, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31352023

RESUMO

Factors that can modify the bioavailability of orally administered vitamin D are not yet widely known. Ergosterol is a common fungal sterol found in food which has a chemical structure comparable to that of vitamin D. This study aimed to investigate the effect of ergosterol on vitamin D metabolism. Therefore, 36 male wild type-mice were randomly subdivided into three groups (n = 12) and received a diet containing 25 µg vitamin D3 and either 0 mg (control), 2 mg or 7 mg ergosterol per kg diet for 6 weeks. To elucidate the impact of ergosterol on hepatic hydroxylation of vitamin D, human hepatoma cells (HepG2) were treated with different concentrations of ergosterol. Concentrations of vitamin D3 and 25-hydroxyvitamin D3 (25(OH)D3) in cells, livers and kidneys of mice and additionally 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) in serum were quantified by LC-MS/MS. The concentration of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in serum was analyzed by commercially-available enzyme immuno assay. The concentrations of cholesterol and triglycerides were analyzed in livers of mice by photometric assays. Analyses revealed that mice receiving 7 mg/kg ergosterol with their diet had 1.3-, 1.7- and 1.5-times higher concentrations of vitamin D3 in serum, liver and kidney, respectively, than control mice (P < 0.05), whereas no significant effects were observed in mice fed 2 mg/kg ergosterol. The hydroxylation of vitamin D remained unaffected by dietary ergosterol, since the concentration of 25-hydroxyvitamin D3 in serum and tissues and the concentrations of 1,25(OH)2D3 and 24,25(OH)2D3 in serum were not different between the three groups of mice. The lipid concentrations in liver were also not affected by dietary ergosterol. Data from the cell culture studies showed that ergosterol did not influence the conversion of vitamin D3 to 25(OH)D3. To conclude, ergosterol appears to be a modulator of vitamin D3 concentrations in the body of mice, without modulating the hydroxylation of vitamin D3 in liver.


Assuntos
Colecalciferol/farmacologia , Ergosterol/farmacologia , Vitaminas/farmacologia , 24,25-Di-Hidroxivitamina D 3/sangue , 24,25-Di-Hidroxivitamina D 3/metabolismo , Animais , Calcifediol/sangue , Calcifediol/metabolismo , Colecalciferol/sangue , Colecalciferol/farmacocinética , Células Hep G2 , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Vitaminas/sangue , Vitaminas/farmacocinética
12.
Arch Anim Nutr ; 73(1): 44-51, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31274343

RESUMO

The study evaluated the effects of different doses of 25-hydroxyvitamin D3 (25(OH)D3) on growth performance, immune function and antioxidative capacity in piglets. In a 21-d trial, 35 weaned pigs were divided into five groups and diets were supplemented with 5.5 (control), 43.0, 80.5, 118.0 and 155.5 µg 25(OH)D3/kg, respectively. No treatment effects were observed for average daily gain, average daily feed intake and feed to gain ratio. Increasing dietary 25(OH)D3 levels increased serum 25(OH)D3 concentrations linearly (p < 0.01), decreased the frequency of CD3+CD4+ and CD3+CD8+ T cells (p < 0.01), and the serum level of complement component 3 (p < 0.05). Supplementation of 80.5 and 118.0 µg 25(OH)D3/kg enhanced the activity of serum glutathione peroxidase (p < 0.05) and addition of 43.0 µg 25(OH)D3/kg increased the malondialdehyde concentration (p < 0.05). Overall, feeding high-dose 25(OH)D3 to weaned pigs partly improved immune functions and the antioxidative capacity.


Assuntos
Antioxidantes/metabolismo , Calcifediol/metabolismo , Imunidade Inata/imunologia , Sus scrofa/fisiologia , Vitaminas/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Calcifediol/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Imunidade Inata/efeitos dos fármacos , Sus scrofa/crescimento & desenvolvimento , Sus scrofa/imunologia , Vitaminas/administração & dosagem , Desmame
13.
Poult Sci ; 98(11): 6108-6116, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31222260

RESUMO

The study aimed to examine the effects of 25-hydroxycholecalciferol (25-OH-D3) on reproductive performance and livability in broiler breeder hens. Hens at age of 26 wk were continued on restricted rations (R) or allowed ad libitum feeding (Ad) to 60 wk of age. Ad-feed intake greatly impaired egg production and hens' livability. The survival rate in both R- and Ad-hens was improved (86.7 vs.78.9% and 48.2 vs.29.1%, respectively) as was egg production in R-hens (P < 0.05) by inclusion of 69 µg 25-OH-D3/kg feedin the basal diet. Sudden death (SD) was the cause of hen mortality; hens died earlier with heavier BW and greater absolute and relative abdominal fat weights than surviving hens. Interestingly, feed intake of SD hens became less than that of surviving hens after 37 and 42 wk in Ad- and R-groups, respectively, and led to a progressive decline in SD hen BW with a ratio (relative to surviving hens of the same age) equaled 1 around 34 to 38 wk in Ad-groups and 52 to 53 wk in R-groups. Supplementation of 25-OH-D3 ameliorated untoward changes of heart and respiratory rate of Ad-survivors after 29 wk (P < 0.05), but had no significant effects on SD AD-hens. In contrast to the surviving counterparts, all SD hens experienced persistently higher respiratory rates in conjunction with declining heart rates (P < 0.05), suggesting compromised cardiac function as the cause of SD, in which hens increased heart and respiratory rate for more blood and oxygen supply to meet the need for rapid BW gain and/or adiposity in response to Ad-feed intake or due to genetically better feed efficiency even under R-feed intake. As the cardiorespiratory derangements advanced, compromised cardiac function ultimately led to heart failure and sudden death despite spontaneous reductions in feed intake and BW loss in all SD hens. Provision of 69 µg 25-OH-D3/kg feed is an effective and practical method to improve livability in broiler breeder hens.


Assuntos
Calcifediol/metabolismo , Galinhas/fisiologia , Longevidade/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Vitaminas/metabolismo , Ração Animal/análise , Animais , Calcifediol/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Feminino , Vitaminas/administração & dosagem
14.
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
15.
Arch Anim Nutr ; 73(4): 271-286, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31192703

RESUMO

To investigate the effects of maternal 25-hydroxycholecalciferol (25OHD3) supplementation during lactation on nutrient digestibility and milk composition of sows and gut bacterial metabolites and their metabolites in the hindgut of suckling piglets, 24 Large White × Landrace sows were assigned randomly to one of two dietary treatments (Diet ND: 2000 IU vitamin D3/kg feed; Diet 25-D: 50 µg 25OHD3/kg feed). The experiment began on d 107 of gestation and continued until weaning on d 21 of lactation. Maternal 25OHD3 supplementation increased (p < 0.05) total litter weight gain during lactation. Milk fat content, immunoglobulin G level on d 21 of lactation and 25OHD3 concentration on d 7, 14, and 21 of lactation were higher (p < 0.05) in sows fed with 25OHD3. Apparent total tract digestibility of dietary calcium was higher (p < 0.05) in 25-D sows than ND sows. With respect to fatty-acid profile, C16:0 and saturated fatty acids in milk were higher (p < 0.05), but C20:4n-6, the ratios of monounsaturated fatty acids to saturated fatty acids and polyunsaturated fatty acids to saturated fatty acids were lower (p < 0.05) in 25-D sows than ND sows. 25OHD3 supplementation increased the mRNA expressions of acetyl-CoA carboxylase α and fatty-acid synthase in the mammary gland of lactating sows. For gut bacterial metabolites, concentration of butyrate in the caecal digesta was higher (p < 0.05) in piglets suckling 25-D sows than piglets suckling ND sows. In conclusion, 25OHD3 supplementation in maternal diets changed dietary calcium digestibility, milk composition and milk fatty-acid profile of lactating sows and altered gut bacterial metabolites in the hindgut of suckling piglets.


Assuntos
Calcifediol/metabolismo , Digestão/fisiologia , Ácidos Graxos/metabolismo , Microbioma Gastrointestinal/fisiologia , Leite/química , Sus scrofa/fisiologia , Vitaminas/metabolismo , Ração Animal/análise , Animais , Animais Lactentes , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Calcifediol/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Digestão/efeitos dos fármacos , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Intestino Grosso/fisiologia , Lactação , Fenômenos Fisiológicos da Nutrição Materna , Leite/efeitos dos fármacos , Nutrientes/metabolismo , Sus scrofa/microbiologia , Vitaminas/administração & dosagem
16.
Nutrients ; 11(5)2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31036792

RESUMO

Salmon have been widely publicized as a good dietary source of vitamin D, but recent data points to large variation in vitamin D content and differences between wild and farmed salmon. We aimed to: (1) investigate the content of vitamin D in Atlantic salmon (Salmo salar) in wild species caught in two different waters, (2) perform a 12-week feeding trial in farmed Salmo salar with 270-1440 µg vitamin D3/kg feed (4-20 times maximum level in the EU) and (3) conduct a review for the published data on the content of vitamin D in salmonids. Content of vitamin D3 in the fillet from wild salmon caught in the Baltic Sea and the North Sea was significantly different (p < 0.05), being 18.5 ± 4.6 µg/100 g and 9.4 ± 1.9 µg/100 g, respectively. In the farmed salmon the content ranged from 2.9 ± 0.7 µg vitamin D3/100 g to 9.5 ± 0.7 µg vitamin D3/100 g. Data from 2018 shows that farmed salmon contained 2.3-7.3 µg vitamin D3/100 g. Information on the content of vitamin D in wild and farmed salmonids is very limited, which calls for further research to ensure a sustainable production of salmon with adequate vitamin D.


Assuntos
Animais Selvagens , Aquicultura , Calcifediol/química , Carne/análise , Animais , Composição Corporal , Calcifediol/metabolismo , Humanos , Músculo Esquelético , Salmo salar/crescimento & desenvolvimento
17.
Nutrients ; 11(5)2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31064117

RESUMO

Hypovitaminosis D is becoming a notable health problem worldwide. A consensus exists among several different medical societies as to the need for adequate levels of vitamin D for bone and general health. The correct method by which to restore normal vitamin D levels is still a matter of debate. Although cholecalciferol remains the most commonly distributed form of vitamin D supplementation worldwide, several drugs with vitamin D activity are available for clinical use, and making the correct selection for the individual patient may be challenging. In this narrative review, we aim to contribute to the current knowledge base on the possible and appropriate use of calcifediol-the 25-alpha-hydroxylated metabolite-in relation to its chemical characteristics, its biological properties, and its pathophysiological aspects. Furthermore, we examine the trials that have aimed to evaluate the effect of calcifediol on the restoration of normal vitamin D levels. Calcifediol is more soluble than cholecalciferol in organic solvents, due to its high polarity. Good intestinal absorption and high affinity for the vitamin-D-binding protein positively affect the bioavailability of calcifediol compared with cholecalciferol. In particular, orally administered calcifediol shows a much shorter half-life than oral cholecalciferol. Most findings suggest that oral calcifediol is about three- to five-fold more powerful than oral cholecalciferol, and that it has a higher rate of intestinal absorption. Accordingly, calcifediol can be particularly useful in treating diseases associated with decreased intestinal absorption, as well as obesity (given its lower trapping in the adipose tissue) and potentially neurological diseases treated with drugs that interfere with the hepatic cytochrome P-450 enzyme system, resulting in decreased synthesis of calcifediol. Up to now, there has not been enough clinical evidence for its use in the context of osteoporosis treatment.


Assuntos
Calcifediol/uso terapêutico , Deficiência de Vitamina D/tratamento farmacológico , Osso e Ossos/metabolismo , Calcifediol/metabolismo , Cálcio/metabolismo , Cálcio/farmacocinética , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Humanos
18.
J Med Chem ; 62(15): 6854-6875, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-30916559

RESUMO

For many individuals, in particular during winter, supplementation with the secosteroid vitamin D3 is essential for the prevention of bone disorders, muscle weakness, autoimmune diseases, and possibly also different types of cancer. Vitamin D3 acts via its metabolite 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] as potent agonist of the transcription factor vitamin D receptor (VDR). Thus, vitamin D directly affects chromatin structure and gene regulation at thousands of genomic loci, i.e., the epigenome and transcriptome of its target tissues. Modifications of 1,25(OH)2D3 at its side-chain, A-ring, triene system, or C-ring, alone and in combination, as well as nonsteroidal mimics provided numerous potent VDR agonists and some antagonists. The nearly 150 crystal structures of VDR's ligand-binding domain with various vitamin D compounds allow a detailed molecular understanding of their action. This review discusses the most important vitamin D analogs presented during the past 10 years and molecular insight derived from new structural information on the VDR protein.


Assuntos
Receptores de Calcitriol/química , Receptores de Calcitriol/metabolismo , Vitamina D/análogos & derivados , Vitamina D/metabolismo , Animais , Calcifediol/análogos & derivados , Calcifediol/metabolismo , Calcitriol/análogos & derivados , Calcitriol/metabolismo , Humanos , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína
19.
Arch Biochem Biophys ; 666: 16-21, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30926433

RESUMO

25-Hydroxyvitamin D3 3-epimerase catalyzes the 3ß â†’ 3α epimerization of 25-hydroxyvitamin D3 (25(OH)D3) producing 3-epi-25-hydroxyvitamin D3 (3-epi-25(OH)D3). 3-Epi-25(OH)D3 is one of the most abundant forms of vitamin D present in the serum. It can be converted to 3-epi-1α,25-dihydroxyvitamin D3 by CYP27B1 which generally displays lower biological activity than 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). The 25(OH)D3 3-epimerase has been poorly characterized to date and the gene encoding it has not been identified. The 3-epimerase has been reported to be present in the microsomal fraction of cells, including liver cells, and to use NADPH as cofactor. It can also act on 1,25(OH)2D3 and 24,25(OH)2D3 forming the 3α-epimers. In this study we have characterized the activity of the 25(OH)D3 3-epimerase in rat and human liver microsomes, using 25(OH)D3 as substrate and HPLC to analyze product formation. For both rat and human liver microsomes the preferred cofactor was NADH, with the rat enzyme displaying a 6-fold greater catalytic efficiency (Vmax/Km) for NADH over that for NADPH. No activity was observed with oxidized cofactor, either NAD+ or NADP+. This was unexpected since the initial step in the epimerization, predicted to be the oxidation of the 3ß-OH to a ketone, would require oxidized cofactor. The rat 3-epimerase in microsomes gave a Km for 25(OH)D3 of 14 µM. The reverse reaction, conversion of 3-epi-25(OH)D3 to 25(OH)D3, was catalyzed by both rat and human liver microsomes but at lower rates than the forward reaction. In conclusion, both rat and human 25-hydroxyvitamin D3 3-epimerase catalyze the reversible interconversion of 25(OH)D3 and 3-epi-25(OH)D3, and use NADH as the preferred cofactor. The lack of requirement for exogenous NAD+ suggests that the enzyme has a tightly bound NAD+ in its active site that is released only upon its reduction.


Assuntos
Calcifediol/metabolismo , Microssomos Hepáticos/enzimologia , Racemases e Epimerases/metabolismo , Animais , Catálise , Feminino , Humanos , Cinética , Masculino , NAD/metabolismo , NADP/metabolismo , Ratos , Ratos Wistar
20.
Sci Rep ; 9(1): 1205, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30718630

RESUMO

Vitamin D and parathyroid hormone (PTH) regulate mineral metabolism and are required to maintain calcium levels. Vitamin D deficiency is common, particularly during pregnancy, and has been associated with hypertensive disorders of pregnancy. We sought to determine whether maternal 25(OH)D, PTH and calcium concentrations at 26 weeks gestation are associated with adverse outcomes of pregnancy and establish whether these differ by ethnicity. This study included 476 White British and 534 Pakistani origin mother-offspring pairs from the Born in Bradford cohort study. We used multinomial or logistic regression to explore the association between vitamin D, PTH and calcium with gestational hypertension (GH), pre-eclampsia (PE), caesarean section (CS), preterm birth (PTB) and small for gestational age (SGA). Pakistani women had lower 25(OH)D (median 13.0 vs 36.0 nmol/L), higher PTH (median 7.7 vs 3.3 pmol/L) and similar calcium concentrations compared to White British women. In Pakistani women, higher concentrations of 25(OH)D were associated with a 60% increased odds of GH, and a 37% reduced odds of SGA; PTH was associated with a 45% reduction in the odds of GH. In White British women, each 1 SD increase in calcium concentration was associated with a 34% increase in developing GH but a 33% reduction in the odds of PTB. Associations with PE and CS were consistent with the null. In conclusion, there are ethnic differences in the associations of 25(OH)D, PTH and calcium with important perinatal outcomes. Future research would benefit from examining the associations of 25(OH)D, PTH and calcium together with a range of perinatal outcomes in order to assess the risk-benefit action of each.


Assuntos
Hormônio Paratireóideo/metabolismo , Complicações na Gravidez/etiologia , Vitamina D/metabolismo , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Calcifediol/metabolismo , Cálcio/metabolismo , Cálcio na Dieta/metabolismo , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/metabolismo , Masculino , Gravidez , Complicações na Gravidez/etnologia , Complicações na Gravidez/fisiopatologia , Nascimento Prematuro/etnologia , Nascimento Prematuro/etiologia , Estudos Prospectivos , Deficiência de Vitamina D/complicações , Vitaminas/metabolismo
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