The Impact of Sex and 25(OH)D Deficiency on Metabolic Function in Mice.
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ABSTRACT:
SUBMITTER: Giblin RJ
PROVIDER: S-EPMC5622745 | biostudies-literature | 2017 Sep
REPOSITORIES: biostudies-literature
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The Impact of Sex and 25(OH)D Deficiency on Metabolic Function in Mice.
Giblin Ryan J RJ Bennett Ellen J EJ Zosky Graeme R GR Dwyer Renée M RM
Nutrients 20170907 9
Both dietary fat and vitamin D deficiency have been linked with increased incidence of non-alcoholic fatty liver disease and insulin resistance. While sex differences in disease prevalence and severity are well known, the impact on disease pathogenesis remains unclear. To further explore the effect of these exposures on metabolic function, C57BL/6 male and female mice were weaned onto one of four diets; low fat vitamin D replete, low fat vitamin D deficient, or two high fat diets, one vitamin D ...[more]
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Project description:BackgroundStudies have revealed the association of vitamin D with specific types of cancer development, however, its correlation with colorectal polyps (CRPs) remains unverified. Our study aimed to investigate the relationship between vitamin D levels, metabolic factors, and CRPs.MethodsA cross-sectional study from 2017 to 2019 involving 1306 participants was conducted to investigate the association among vitamin D levels, metabolic factors, uric acid and CRPs in Taiwan. CRPs diagnoses were determined via colonoscopies conducted by experienced gastrointestinal physicians, and biopsied polyps were inspected under a microscope by experienced pathologists. We employed both simple and multiple logistic regression analyses to identify significant factors associated with CRPs and adenomatous polyps, respectively.ResultsOur result showed that the prevalence of 25(OH)-vitamin D deficiency (≦ 20 ng/mL) and CRPs was 21.21% and 40.89%, respectively. Multiple logistic regression revealed that the risk of CRPs increased with old age, male sex, hyperglycemia, high triglyceride levels, and low 25(OH)D levels after adjustment for other factors. Besides, low 25(OH)D levels were significantly associated with CRPs risk in women, whereas elevated blood pressure was associated with CRPs risk in men. 25(OH)D Deficiency was revealed to be significantly associated with risk of CRPs in adults over 50 years old. Compared to nonadenomatous polyps, older age, higher 25(OH) vitamin D and higher uric acid levels were at increased risk for adenomatous polyps.ConclusionsOur study revealed that vitamin D deficiency was significantly associated with the risk of CRPs, especially in adults over 50 years old and women. We should therefore be concerned about the CRP risk of vitamin D deficiency and metabolic syndrome (especially hyperglycemia, elevated blood pressure in men, and high triglyceride levels) in this population.
| S-EPMC10249833 | biostudies-literature
Project description:Cholangiocarcinoma (CCA) is a devastating disease without effective treatments. 1?,25(OH)?D?, the active form of Vitamin D, has emerged as a new anti-cancer regimen. However, the side effect of hypercalcemia impedes its systemic administration. 25(OH)D is biologically inert and needs hydroxylation by CYP27B1 to form 1?,25(OH)?D?, which is originally believed to only take place in kidneys. Recently, the extra-renal expression of CYP27B1 has been identified and in vitro conversion of 25(OH)D to 1?,25(OH)?D? has been found in some cancer cells with CYP27B1 expression. In this study, CYP27B1 expression was demonstrated in CCA cells and human CCA specimens. 25(OH)D effectively represses SNU308 cells growth, which was strengthened or attenuated as CYP27B1 overexpression or knockdown. Lipocalcin-2 (LCN2) was also found to be repressed by 25(OH)D. After treatment with 800 ng/mL 25(OH)D, the intracellular 1?,25(OH)?D? concentration was higher in SNU308 cells with CYP27B1 overexpression than wild type SNU308 cells. In a xenograft animal experiment, 25(OH)D, at a dose of 6 ?g/kg or 20 ?g/kg, significantly inhibited SNU308 cells' growth without inducing obvious side effects. Collectively, our results indicated that SNU308 cells were able to convert 25(OH)D to 1?,25(OH)?D? and 25(OH)D CYP27B1 gene therapy could be deemed as a promising therapeutic direction for CCA.
| S-EPMC5000723 | biostudies-literature
Project description:RationalePatients with chronic rhinosinusitis with nasal polyps (CRSwNP) have been shown to be vitamin D3 (VD3) deficient, which is associated with more severe disease and increased polyp size. To gain mechanistic insights into these observational studies, we examined the impact of VD3 deficiency on inflammation and VD3 metabolism in an Aspergillus fumigatus (Af) mouse model of chronic rhinosinusitis (Af-CRS).MethodsBalb/c mice were fed control or VD3 deficient diet for 4 weeks. Mice were then sensitized with intraperitoneal Af, and one week later given Af intranasally every three days for four weeks while being maintained on control or VD3 deficient diet. Airway function, sinonasal immune cell infiltrate and sinonasal VD3 metabolism profiles were then examined.ResultsMice with VD3 deficiency had increased Penh and sRaw values as compared to controls as well as exacerbated changes in sRaw when coupled with Af-CRS. As compared to controls, VD3 deficient and Af-CRS mice had reduced sinonasal 1α-hydroxylase and the active VD3 metabolite, 1,25(OH)2D3. Differential analysis of nasal lavage samples showed that VD3 deficiency alone and in combination with Af-CRS profoundly upregulated eosinophil, neutrophil and lymphocyte numbers. VD3 deficiency exacerbated increases in monocyte-derived dendritic cell (DC) associated with Af-CRS. Conversely, T-regulatory cells were decreased in both Af-CRS mice and VD3 deficient mice, though coupling VD3 deficiency with Af-CRS did not exacerbate CD4 or T-regulatory cells numbers. Lastly, VD3 deficiency had a modifying or exacerbating impact on nasal lavage levels of IFN-γ, IL-6, IL-10 and TNF-α, but had no impact on IL-17A.ConclusionsVD3 deficiency causes changes in sinonasal immunity, which in many ways mirrors the changes observed in Af-CRS mice, while selectively exacerbating inflammation. Furthermore, both VD3 deficiency and Af-CRS were associated with altered sinonasal VD3 metabolism causing reductions in local levels of the active VD3 metabolite, 1,25(OH)2D3, even with adequate circulating levels.
| S-EPMC5646812 | biostudies-literature
Project description:In addition to its canonical role in musculoskeletal health, several reports have demonstrated that serum vitamin D level may influence kidney function. However, the effect of pretransplant serum vitamin D level on subsequent graft function has not been explored. Therefore, this study was undertaken to examine the effect of serum vitamin D level at the time of kidney transplantation (KT) on subsequent graft function.We analyzed 106 patients who underwent KT and for whom 25-hydroxy vitamin D (25-OHD) levels were measured during hospitalization prior to transplantation. We measured estimated glomerular filtration rates (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula at baseline and at six-month intervals up to 36 months after KT.38.7% of the patients were diagnosed with 25-OHD deficiency defined as less than 10 ng/mL. Recipient gender (female vs. male, odds ratio [OR] 3.30, 95% CI 1.33-8.21, P=0.010), serum albumin level (per 1 mg/dl increase, OR 0.35, 95% CI 0.13-0.98, P=0.047), and predominant renal replacement therapy modality before KT (P<0.001) were found to be independent pretransplant risk factors for 25-OHD deficiency by multivariate logistic regression analysis. Subsequent repeated measures analysis of covariance revealed that 25-OHD level had the only significant main effect on eGFR during the 36-month follow-up period [F (1, 88)=12.07, P=0.001].Pretransplant 25-OHD deficiency was significantly associated with a lower post-transplant eGFR, suggesting that 25-OHD may play an important role in maintaining graft function after KT.
| S-EPMC3393620 | biostudies-literature
Project description:STUDY QUESTION:Is pre-conception 25(OH)D associated with the per cycle probability of conception, i.e fecundability, in a prospective cohort study? SUMMARY ANSWER:There are suggestive associations of high 25(OH)D (at least 50 ng/ml) with increased fecundability and low 25(OH)D (<20 ng/ml) with reduced fecundability, but the estimates were imprecise. WHAT IS KNOWN ALREADY:Vitamin D has been associated with reproductive function and fertility in animal studies, but few human studies exist. STUDY DESIGN, SIZE, DURATION:This community-based prospective cohort study included 522 women attempting to become pregnant between 2010 and 2016. The women completed online daily and monthly diaries until a positive home pregnancy test was observed or 12 months had elapsed. PARTICIPANTS/MATERIALS, SETTING, METHODS:The study included women from central North Carolina who were aged 30-44 with no history of infertility, with no more than 3 months of attempt time at recruitment. Women recorded vaginal bleeding so that the ongoing number of attempt cycles could be counted and used to quantify a woman's pregnancy attempt time. Blood collected at the study entry was analysed for 25(OH)D using liquid chromatography tandem mass spectrometry. Associations with fecundability were estimated with a log-binomial discrete time-to-event model. MAIN RESULTS AND THE ROLE OF CHANCE:Among 522 women, 257 conceived during the study. The mean age was 33 years and the mean 25(OH)D was 36 ng/ml. There was an estimated 10% higher fecundability with each 10 ng/ml increase in 25(OH)D (fecundability ratio (FR) 1.10, 95% CI: 0.96, 1.25). The suggestive dose-response association with the continuous measure of 25(OH)D was driven by women in the lowest and the highest categories of 25(OH)D. Compared to women with 25(OH)D of 30-40 ng/ml, women below 20 ng/ml had an estimated 45% reduction in fecundability (FR (CI): 0.55 (0.23, 1.32)), and women with at least 50 ng/ml had an estimated 35% increase in fecundability (FR (CI): 1.35 (0.95, 1.91)). Across these three categories (25(OH)D of <20 ng/ml, 30-40 ng/ml and?>?50 ng/ml), the probability of taking longer than 6 months to conceive was, respectively, 51% (17%, 74%), 28% (17%, 39%) and 15% (10%, 37%). LIMITATIONS, REASONS FOR CAUTION:While the distribution of 25(OH)D was wide, the number of observed cycles with high 25(OH)D (N?=?107) or low 25(OH)D (N?=?56) was small. WIDER IMPLICATIONS OF THE FINDINGS:Our findings are consistent with prior reports of reduced fertility in women with 25(OH)D concentrations below the clinically defined deficiency level (20 ng/ml). Further studies are needed to evaluate the possible reproductive benefits of considerably higher 25(OH)D concentration (>50 ng/ml). STUDY FUNDING/COMPETING INTEREST(S):This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH) under award numbers R00HD079659 and R01HD067683 and supported in part by the Intramural Research Program of the National Institute of Environmental Health Sciences, under projects ES103086, ES049003 and ES044003. ClearBlue ovulation predictor kits were generously donated to AMZJ and AJW by Swiss Precision Diagnostics. Drs Wilcox and Jukic report non-financial support from Swiss Precision Diagnostics during the conduct of the study; Dr Jukic reports non-financial support from Theralogix, LLC, outside the submitted work. Otherwise there are no competing interests. TRIAL REGISTRATION NUMBER:N/A.
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Project description:ObjectiveTo analyze the associations between serum 25(OH)D levels and the risk of metabolic syndrome (MetS) and its components, and the related genetic and non-genetic factors in non-diabetic women of childbearing age in China.MethodsSubjects were randomly selected from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. The data of sociodemographic characteristics and lifestyle factors were obtained through questionnaire survey. Anthropometry was measured by trained interviewers, and fasting blood was collected to test 25-hydroxyvitamin D [25(OH)D], total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), and other related parameters. Generalized linear mode and multivariate logistic analysis were performed to analyze the associations between serum 25(OH)D and MetS and its components, adjusting for the possible confounders.ResultsBody mass index (BMI), serum alanine aminotransferase (ALT), hypersensitive C-reactive protein (hs-CRP), 25(OH)D, phosphorus (P), and parathyroid hormone (PTH) levels were associated with the number of MetS's components. G allele carriers of GC rs2282679 had higher diastolic blood pressure (DBP) and FBG levels compared with the TT genotypes, while higher genetic risk score (GRS) seemed to be associated with reduced HDL-C level. The odds ratio (OR) for MetS in lowest group of 25(OH)D was 1.533 (0.980-2.399) after adjusting for season, district, area type, latitude, age, BMI, PTH, P, ALT, CRE, interleukin-6 (IL-6), and hs-CRP, compared with the median group, but the association was not significant. An insufficient 25(OH)D concentration (<14.22 ng/mL) was significantly related to the risk of elevated waist circumference (WC) (OR = 1.612 (1.014-2.561)) and TG (OR = 2.210 (1.318-3.706)), and reduced HDL-C (OR = 1.639 (1.206-2.229)) after adjusting for the confounders among these women. Moreover, these relationships were not affected by vitamin D metabolism-related gene polymorphisms.ConclusionAfter comprehensively considering various influencing factors, significant associations between insufficient serum 25(OH)D and MetS's components, including elevated WC, TG, and reduced HDL-C, were observed. However, MetS, hypertension, and hyperglycemia were not found independently associated with 25(OH)D levels.
| S-EPMC9182986 | biostudies-literature
Project description:Obesity is associated to chronic low-grade metabolic inflammation and hypovitaminosis D. Among extra-skeletal effects, an important role in inflammation has been described for vitamin D (25(OH)D). Phase angle (PhA) is a bioelectrical impedance analysis (BIA) parameter that represents an indicator of cellular health in chronic inflammatory states. However, it is still unknown whether a low 25(OH)D levels might correlate with PhA in obesity. Considering the lack of evidence correlating the 25(OH)D levels with PhA in obesity, the aim of this study was to investigate their possible relationship in a group of patients with obesity stratified according to body mass index (BMI) categories. Four hundred and fifty-five adult subjects (219 males and 236 females; 36 ± 11 years) were enrolled. Body composition, including PhA, was assessed using a BIA phase-sensitive system. Serum levels of 25(OH)D was determined by a direct competitive chemiluminescence immunoassay. Most of the participants were affected by grade III obesity (24%) and had 25(OH)D deficiency (67%). Subjects with 25(OH)D deficiency had highest BMI (p < 0.001). Stratifying the sample population according to the BMI classes, 25(OH)D levels decreased significantly along with the increase in BMI (p < 0.001), with the lowest 25(OH)D levels in the class III obesity. In addition, stratifying the sample population according to 25(OH)D categories, BMI and fat mass (FM) decreased, while PhA increased significantly along with the 25(OH)D categories (p < 0.001). The 25(OH)D levels showed significant positive associations with PhA (r = -0.59, p < 0.001), and this association remained significant also after adjusting for BMI and FM (r = 0.60, p < 0.001). The lowest values of PhA were significantly associated with the severity of obesity (OR 0.3, p < 0.001) and of 25(OH)D deficiency (OR 0.2, p < 0.001). To compare the relative predictive power of body composition parameters associated with the 25(OH)D levels, we performed a multiple linear regression analysis. The most sensitive and specific cut-off for 25(OH)D levels to predict the PhA above the median was >14 ng/mL (p < 0.001). In conclusion, we provided preliminary insights into a novel link between 25(OH)D levels and PhA in the setting of obesity. This association uncovered a new potential usefulness of PhA as expression of cell membrane integrity and predictor of inflammation in low 25(OH)D status that might help in identifying high-risk patients with obesity who could benefit from careful 25(OH)D supplementation.
| S-EPMC6723101 | biostudies-literature
Project description:OBJECTIVE:The aim of the study was to examine the associations between 25-hydroxyvitamin D (25(OH)D) and biomarkers of ovarian reserve in a large community-based sample of women. METHODS:In 2010 to 2016, women aged 30 to 44 years without any known fertility problems were recruited from the Chapel Hill, NC area for a prospective time-to-pregnancy cohort study. At enrollment 561 women provided a blood sample that was used to measure 25(OH)D, anti-Müllerian hormone (AMH), follicle-stimulating hormone, and inhibin-B. Unadjusted associations were estimated with Spearman correlation coefficients. Multivariable linear regression was used to estimate associations of 25(OH)D with ovarian reserve biomarkers, after adjusting for age, race, body mass index, smoking history, and recent use of hormonal birth control. RESULTS:The mean 25(OH)D was 36?ng/mL (SD?=?11?ng/mL). 25(OH)D was not correlated with AMH, follicle-stimulating hormone, or inhibin-B (all r?<?0.03). Multivariable results with continuous hormonal outcomes were also null. For dichotomous outcomes, there was a tendency for insufficient 25(OH)D (<30?ng/mL) to be associated with low AMH (<0.7?ng/mL) (odds ratio [95% CI]: 1.8 [0.9-4]). CONCLUSIONS:For the most part, 25(OH)D was not associated with ovarian reserve biomarkers in a group of women trying to become pregnant. We found some evidence that low 25(OH)D (<30?ng/mL) was associated with low AMH, but this should be confirmed in studies with a higher prevalence of low 25(OH)D.
| S-EPMC6014875 | biostudies-literature
Project description:Abstract Objectives An important point of contention is whether genetic variation has meaningful impact on vitamin D adequacy on top of known modulators like season, fat mass, skin pigmentation and geographic latitude. Answers could come from information generated by numerous published studies. As a first step towards integration of these often diverse data, the impact of the commonly measured single nucleotide variant rs4588 of the GC gene on 25-hydroxy vitamin D (25OHD) concentration in blood of healthy Caucasian adults was assessed with a systematic review and metaanalysis of published findings. Methods Selection criteria for inclusion of studies in the analyses were Caucasian healthy adults and listing of average 25OHD concentration in plasma or serum by rs4588 or the tightly linked rs2282679 genotypes. Percent differences between genotypes were extracted from included publications. A random-effects model of metaanalysis was performed using STAT 16. Results Of the studies meeting inclusion criteria, published between 2005 and 2019, 35 reported genotype-specific 25OHD concentrations in a total of 59,939 Caucasian adults. The weighted averages were 25.3, 23.2 and 20.4 ng/ml for the GC rs4588 CC, AC and AA genotypes. Relative differences are more informative than absolute concentrations since they are much less affected by calibration discrepancies. The CA carriers had 6.8% lower concentrations than CC carriers and AA carriers 15% lower concentrations when using averages weighted by cohort size. Eight of the included studies with a total number of 15,329 individuals reported standard deviations for the genotype-specific 25OHD concentrations and only these were included for the metaanalysis. The average effect size was −0.44 (95% CI; −0.89, 0.01) for carriers of a single rs4588 A allele, and −0.59 (95% CI; −0.94, −0.23) for carriers of two AA alleles. Heterogeneity was high and statistically significant. Conclusions The combined data indicate that 25OHD concentrations differ by GC rs4588 genotype in healthy adults with predominantly Caucasian ancestry with an additive effect of about 9% per allele. The much lower than average 25OHD concentrations in the about 8% GC rs4588 AA genotype carriers should draw attention to this commonly ignored group when it comes to health risks related to vitamin D deficiency. Funding Sources UNC Nutrition Research Institute internal support
| S-EPMC8181666 | biostudies-literature
Project description:ContextThe optimal measure of vitamin D status is unknown.ObjectiveTo directly measure circulating free 25-hydroxyvitamin D [25(OH)D] concentrations and relationships to total 25(OH)D in a clinically diverse sample of humans.DesignCross-sectional analysis.SettingSeven academic sites.PatientsA total of 1661 adults: healthy (n = 279), prediabetic (n = 479), outpatients (n = 714), cirrhotic (n = 90), pregnant (n = 20), nursing home resident (n = 79).InterventionsMerge research data on circulating free 25(OH)D (directly-measured immunoassay), total 25(OH)D (liquid chromatography/tandem mass spectrometry), D-binding protein [DBP; by radial (polyclonal) immunodiffusion assay], albumin, creatinine, intact parathyroid hormone, and DBP haplotype.Main outcome measuresDistribution of free 25(OH)D (ANOVA with Bonferroni correction for post hoc comparisons) and relationships between free and total 25(OH)D (mixed-effects modeling incorporating clinical condition, DBP haplotype with sex, race, estimated glomerular filtration rate (eGFR), body mass index (BMI), and other covariates).ResultsFree 25(OH)D was 4.7 ± 1.8 pg/mL (mean ± SD) in healthy persons and 4.3 ± 1.9 pg/mL in outpatients, with levels of 0.5 to 8.1 pg/mL and 0.9 to 8.1 pg/mL encompassing 95% of healthy persons and outpatients, respectively. Free 25(OH)D was higher in patients with cirrhosis (7.1 ± 3.0 pg/mL; P < 0.0033) and nursing home residents (7.9 ± 2.1 pg/mL; P < 0.0033) than in other groups and differed between whites and blacks (P < 0.0033) and between DBP haplotypes (P < 0.0001). Mixed-effects modeling of relationships between free and total 25(OH)D identified clinical conditions (patients with cirrhosis > nursing home residents > patients with prediabetes > outpatients > pregnant women) and BMI (lesser effect) as covariates affecting relationships but not eGFR, sex, race, or DBP haplotype.ConclusionsTotal 25(OH)D, health condition, race, and DBP haplotype affected free 25(OH)D, but only health conditions and BMI affected relationships between total and free 25(OH)D. Clinical importance of free 25(OH)D needs to be established in studies assessing outcomes.
| S-EPMC6126881 | biostudies-literature