scholarly journals Long-Term Fgf23 Deficiency Does Not Influence Aging, Glucose Homeostasis, or Fat Metabolism in Mice with a Nonfunctioning Vitamin D Receptor

Endocrinology ◽  
2012 ◽  
Vol 153 (4) ◽  
pp. 1795-1805 ◽  
Author(s):  
Carmen Streicher ◽  
Ute Zeitz ◽  
Olena Andrukhova ◽  
Anne Rupprecht ◽  
Elena Pohl ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Fat Mass ◽  
Fibroblast Growth Factor 23 ◽  
Pancreatic Beta Cell ◽  
Fat Metabolism ◽  
Premature Aging ◽  
Mutant Mice ◽  
Whole Body ◽  
Beta Cell Volume

It is still controversial whether the bone-derived hormone fibroblast growth factor-23 (FGF23) has additional physiological functions apart from its well-known suppressive actions on renal phosphate reabsorption and vitamin D hormone synthesis. Here we analyzed premature aging, mineral homeostasis, carbohydrate metabolism, and fat metabolism in 9-month-old male wild-type (WT) mice, vitamin D receptor mutant mice (VDRΔ/Δ) with a nonfunctioning vitamin D receptor, and Fgf23−/−/VDRΔ/Δ compound mutant mice on both a standard rodent chow and a rescue diet enriched with calcium, phosphorus, and lactose. Organ atrophy, lung emphysema, and ectopic tissue or vascular calcifications were absent in compound mutants. In addition, body weight, glucose tolerance, insulin tolerance, insulin secretory capacity, pancreatic beta cell volume, and retroperitoneal and epididymal fat mass as well as serum cholesterol and triglycerides were indistinguishable between vitamin D receptor and compound mutants. In contrast to VDRΔ/Δ and Fgf23−/−/VDRΔ/Δ mice, which stayed lean, WT mice showed obesity-induced insulin resistance. To rule out alopecia and concomitantly elevated energy expenditure present in 9-month-old VDRΔ/Δ and Fgf23−/−/VDRΔ/Δ mice as a confounding factor for the lacking effect of Fgf23 deficiency on fat mass, we analyzed whole-body composition in WT, Fgf23−/−, VDRΔ/Δ, and Fgf23−/−/VDRΔ/Δ mice at the age of 4 wk, when the coat in VDRΔ/Δ mice is still normal. Whole-body fat mass was reduced in Fgf23−/− mice but almost identical in WT, VDRΔ/Δ, and Fgf23−/−/VDRΔ/Δ mice. In conclusion, our data indicate that Fgf23 has no molecular vitamin D-independent role in aging, insulin signaling, or fat metabolism in mice.

scholarly journals Involvement of the vitamin D receptor in energy metabolism: regulation of uncoupling proteins

2009 ◽  
Vol 296 (4) ◽  
pp. E820-E828 ◽  
Author(s):  
Kari E. Wong ◽  
Frances L. Szeto ◽  
Wenshuo Zhang ◽  
Honggang Ye ◽  
Juan Kong ◽  
...  
Keyword(s):  
Vitamin D ◽  
Energy Metabolism ◽  
Energy Expenditure ◽  
Vitamin D Receptor ◽  
Fat Mass ◽  
Uncoupling Protein ◽  
Mutant Mice ◽  
Metabolism Regulation ◽  
Null Mutant Mice

Recent studies have established that vitamin D plays multiple biological roles beyond calcium metabolism; however, whether vitamin D is involved in energy metabolism is unknown. To address this question, we characterized the metabolic phenotypes of vitamin D receptor (VDR)-null mutant mice. Under a normocalcemic condition, VDR-null mice displayed less body fat mass and lower plasma triglyceride and cholesterol levels compared with wild-type (WT) mice; when placed on a high-fat diet, VDR-null mice showed a slower growth rate and accumulated less fat mass globally than WT mice, even though their food intake and intestinal lipid transport capacity were the same as WT mice. Consistent with the lower adipose mass, plasma leptin levels were lower and white adipocytes were histologically smaller in VDR-null mice than WT mice. The rate of fatty acid β-oxidation in the white adipose tissue was higher, and the expression of uncoupling protein (UCP) 1, UCP2 and UCP3 was markedly upregulated in VDR-null mice, suggesting a higher energy expenditure in the mutant mice. Experiments using primary brown fat culture confirmed that 1,25-dihydroxyvitamin D3 directly suppressed the expression of the UCPs. Consistently, the energy expenditure, oxygen consumption, and CO2 production in VDR-null mice were markedly higher than in WT mice. These data indicate that vitamin D is involved in energy metabolism and adipocyte biology in vivo in part through regulation of β-oxidation and UCP expression.

Premature aging in vitamin D receptor mutant mice

2009 ◽  
Vol 115 (3-5) ◽  
pp. 91-97 ◽  
Author(s):  
Tiina Keisala ◽  
Anna Minasyan ◽  
Yan-Ru Lou ◽  
Jing Zou ◽  
Allan V. Kalueff ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Premature Aging ◽  
Mutant Mice ◽  
Receptor Mutant

scholarly journals Genetic variation in the human vitamin D receptor is associated with muscle strength, fat mass and body weight in Swedish women

2004 ◽  
pp. 323-328 ◽  
Author(s):  
E Grundberg ◽  
H Brandstrom ◽  
EL Ribom ◽  
O Ljunggren ◽  
H Mallmin ◽  
...  
Keyword(s):  
Vitamin D ◽  
Body Weight ◽  
Genetic Variation ◽  
Muscle Strength ◽  
Body Mass ◽  
Vitamin D Receptor ◽  
Fat Mass ◽  
Restriction Site ◽  
Mineral Density ◽  
Healthy Women

OBJECTIVE: Bone mineral density (BMD) is under strong genetic control and a number of candidate genes have been associated with BMD. Both muscle strength and body weight are considered to be important predictors of BMD but far less is known about the genes affecting muscle strength and fat mass. The purpose of this study was to investigate the poly adenosine (A) repeat and the BsmI SNP in the vitamin D receptor (VDR) in relation to muscle strength and body composition in healthy women. DESIGN: A population-based study of 175 healthy women aged 20-39 years was used. METHODS: The polymorphic regions in the VDR gene (the poly A repeat and the BsmI SNP) were amplified by PCR. Body mass measurements (fat mass, lean mass, body weight and body mass index) and muscle strength (quadriceps, hamstring and grip strength) were evaluated. RESULTS: Individuals with shorter poly A repeat, ss and/or absence of the linked BsmI restriction site (BB) have higher hamstring strength (ss vs LL, P=0.02), body weight (ss vs LL, P=0.049) and fat mass (ss vs LL, P=0.04) compared with women with a longer poly A repeat (LL) and/or the presence of the linked BsmI restriction site (bb). CONCLUSIONS: Genetic variation in the VDR is correlated with muscle strength, fat mass and body weight in premenopausal women. Further functional studies on the poly A microsatellite are needed to elucidate whether this is the functionally relevant locus or if the polymorphism is in linkage disequilibrium with a functional variant in a closely situated gene further downstream of the VDR 3'UTR.

scholarly journals Serum levels of 25 (OH) vitamin D in adults with obesity sarcopenia

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Maria Nikolova ◽  
Alexander Penkov
Keyword(s):  
Vitamin D ◽  
Body Composition ◽  
Fat Mass ◽  
Lean Mass ◽  
Fat Free Mass ◽  
Whole Body ◽  
Composition Analysis ◽  
Appendicular Lean Mass ◽  
Vitamin D Levels ◽  
25 Oh Vitamin D

AbstractIntroduction:Obesity has been linked with vitamin D deficiency in a number of cross-sectional studies, reviews and meta-analyses. To assess the correlations of plasma 25(OH) vitamin D levels with indices of body composition examined by DXA with an emphasis on lean and bone mass as well as on indices such as android/gynoid fat, appendicular lean mass (ALM) and appendicular lean mass index (ALMI), fat-mass indexes (FMI), fat-free mass indexes (FFMI) and the ALM-to-BMI index.Materials and Methods:62 adult subjects consented to participate – 27 men (43.5 %) and 35 women (56.5 %). Their mean age was 45.3 ± 9.5 years. Fan-beam dual-energy X-ray (DXA) body composition analysis was performed on a Lunar Prodigy Pro bone densitometer with software version 12.30. Vitamin D was measured by electro-hemi-luminescent detection as 25(OH)D Total (ECLIA, Elecsys 2010 analyzer, Roche Diagnostics). Statistical analyses were done using the SPSS 23.0 statistical package.Results:The serum 25(OH)D level was correlated significantly only to the whole body bone mineral content, the appendicular lean mass index (ALMI) and the ALM-to-BMI index, underlining a predominant role for lean and fat-free mass. Vitamin D showed a very weak correlation to % Body Fat and the Fat Mass Index (FMI) in men only. Moreover, the multiple regression equation including the associated parameters could explain only 7 % of the variation in the serum 25(OH)D levels.Discussion:Our conclusion was, that there are differences in the associations of the vitamin D levels with the different body composition indices, but these associations are generally very weak and therefore – negligible.

scholarly journals Premature aging‐like phenotype in fibroblast growth factor 23 null mice is a vitamin D‐mediated process

2006 ◽  
Vol 20 (6) ◽  
pp. 720-722 ◽  
Author(s):  
Mohammed S. Razzaque ◽  
Despina Sitara ◽  
Takashi Taguchi ◽  
René St‐Arnaud ◽  
Beate Lanske
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Premature Aging ◽  
Fibroblast Growth

scholarly journals Role of the vitamin D receptor in FGF23 action on phosphate metabolism

2005 ◽  
Vol 390 (1) ◽  
pp. 325-331 ◽  
Author(s):  
Yoshio Inoue ◽  
Hiroko Segawa ◽  
Ichiro Kaneko ◽  
Setsuko Yamanaka ◽  
Kenichiro Kusano ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Fibroblast Growth Factor 23 ◽  
Mrna Levels ◽  
Dna Encoding ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Naked Dna ◽  
25 Hydroxyvitamin D

FGF23 (fibroblast growth factor 23) is a novel phosphaturic factor that influences vitamin D metabolism and renal re-absorption of Pi. The goal of the present study was to characterize the role of the VDR (vitamin D receptor) in FGF23 action using VDR(−/−) (VDR null) mice. Injection of FGF23M (naked DNA encoding the R179Q mutant of human FGF23) into VDR(−/−) and wildtype VDR(+/+) mice resulted in an elevation in serum FGF23 levels, but had no effect on serum calcium or parathyroid hormone levels. In contrast, injection of FGF23M resulted in significant decreases in serum Pi levels, renal Na/Pi co-transport activity and type II transporter protein levels in both groups when compared with controls injected with mock vector or with FGFWT (naked DNA encoding wild-type human FGF23). Injection of FGF23M resulted in a decrease in 25-hydroxyvitamin D 1α-hydroxylase mRNA levels in VDR(−/−) and VDR(+/+) mice, while 25-hydroxyvitamin D 24-hydroxylase mRNA levels were significantly increased in FGF23M-treated animals compared with mock vector control- or FGF23WT-treated animals. The degree of 24-hydroxylase induction by FGF23M was dependent on the VDR, since FGF23M significantly reduced the levels of serum 1,25(OH)2D3 [1,25-hydroxyvitamin D3] in VDR(+/+) mice, but not in VDR(−/−) mice. We conclude that FGF23 reduces renal Pi transport and 25-hydroxyvitamin D 1α-hydroxylase levels by a mechanism that is independent of the VDR. In contrast, the induction of 25-hydroxyvitamin D 24-hydroxylase and the reduction of serum 1,25(OH)2D3 levels induced by FGF23 are dependent on the VDR.

scholarly journals Correction of Low Neonatal Vitamin D Status Using 1000 IU/d of Vitamin D Improved Body Composition (Lean Mass and Fat Mass) Compared to Using the Standard of Care by 6 Months of Age (P11-094-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Maryam Razaghi ◽  
Catherine Vanstone ◽  
Olusola Sotunde ◽  
Nathalie Gharibeh ◽  
Sarah Kimmins ◽  
...  
Keyword(s):  
Vitamin D ◽  
Body Composition ◽  
Fat Mass ◽  
Lean Mass ◽  
Gestational Age ◽  
Skin Color ◽  
Reference Group ◽  
Combined Treatment ◽  
Whole Body ◽  
Vitamin D Status

Abstract Objectives Vitamin D status is positively associated with lean mass phenotype in healthy infants born with sufficient vitamin D stores. The objective is to test whether rapid correction of low neonatal vitamin D status improves body composition (lean mass and fat mass) at 6 mo of age. Methods In a double-blinded randomized parallel group controlled trial (NCT02563015), healthy term neonates of appropriate weight for gestational age were recruited from Montreal. Capillary blood samples were collected 24–36 h post natally for measurement of serum 25-hydroxyvitamin D [25(OH)D] (Liaison, Diasorin Inc.). Infants with serum 25(OH)D < 50 nmol/L (n = 87) were randomized to receive 400 or 1000 IU/d until 6 mo of age. Those with 25(OH)D ≥ 50 nmol/L (n = 31) were recruited as a reference group, and received 400 IU/d. Anthropometry, lean mass and fat mass (dual-energy x-ray absorptiometry) were measured at baseline, 3 and 6 mo. Skin color was measured using a spectrophotometer. Differences between treatments and reference groups were tested using mixed model and repeated measures ANOVA accounting for the effects of sex, season of birth, skin color and gestational age (GA). Results Neonates (67 males, 51 females) were 39.6 ± 1wk GA and 3387 ± 371 g at birth. There were no differences between groups in lean mass or fat mass at baseline; nor in weight or length at any time-point. Combined treatment groups, had lower serum 25(OH)D concentrations at birth compared to the reference group (33 ± 11 vs. 69 ± 13 nmol/L, P < 0.0001). However, at 6 mo of age, serum 25(OH)D concentration was higher in the group receiving 1000 IU/d (n = 34), in comparison to the group receiving 400 IU/d (n = 29), and the reference (n = 19) group (125.0 ± 34.0, 82.2 ± 21.5 vs. reference 85.4 ± 32.1 nmol/L, P < 0.0001). Whole body lean mass was significantly different among groups (5071.3 ± 750.0, 4944.1 ± 616.3 and 5166.0 ± 645.4 g, respectively, P = 0.03), with infants in the treatment group provided a 400 IU/d supplement having a lower lean mass by 6 mo of age compared to the 1000 IU/d group. Fat mass was not different among groups following post-hoc testing (2967.0 ± 929.0 and 2962.0 ± 952.0, 2742.0 ± 754.0 g, P = 0.16). Conclusions Higher dosage supplementation of vitamin D rapidly improved vitamin D status and supported a leaner body phenotype in infancy. Funding Sources Canadian Institutes of Health Research.

Oxidative Stress, Vitamin D Deficiency and Male Infertility: An Under-Looked Aspect

2021 ◽  
pp. 1-3
Author(s):  
Maheen Shahid ◽  
Syeda Amrah Hashmi ◽  
Rehana Rehman ◽  
Admin
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Male Infertility ◽  
Vitamin D Deficiency ◽  
Vitamin D Receptor ◽  
Calcium Supplementation ◽  
Mutant Mice ◽  
Aromatase Activity ◽  
Vitamin D Receptors ◽  
Gonadal Dysfunction

Dear Madam, Infertility is a known source of distress among couples worldwide. This agony significantly stems from the concern of not having an identifiable cause leading to infertility. With male factors accounting for 20-30% of the total causes of infertility (1), a thorough evaluation of both the partners is done. Upon evaluation, Vitamin D deficiency was noticed significantly in males coming to infertility centres. However, its functions and how it impacted reproduction was not known until the research led to the discovery of Vitamin D Receptor (VDR) in many organs of the male reproductive tract. It is now known that vitamin D deficiency decreases male fertility by contributing to oxidative stress and gonadal insufficiency, disrupting spermatogenesis, affecting sperm morphology and normal calcium haemostasis. (2) Oxidative stress, caused by an imbalance between oxidative and antioxidative mechanisms, is believed to be a well-known mechanism underlying idiopathic male infertility. Reproductive health professionals and researchers fittingly started searching for antioxidants to combat this imbalance. A study concluded that adding vitamin D to a cryopreserved semen sample reduced oxidative stress and resulted in better fertility outcomes (3). Animal trials have shown that Vitamin D supplementation reduced oxidative stress and improved semen DNA integrity (4). As Vitamin D exerts its effects by binding to Vitamin D receptors, it was noted that vitamin D receptor null mutant mice had a significant reduction in successful reproductive outcomes due to gonadal insufficiencies. Reduced levels of oestrogen and testosterone were seen along with low sperm count, reduced motility, abnormal spermatogenesis and histological abnormalities in testes of mutant mice. These insufficiencies were attributed to a decreased CYP2R1, CYP27B1 and CYP24A1 expression, lower aromatase activity, secondary to suppression of CYP19 gene and calcium supplementation improved fertility in such cases. (5) There is limited human data available on how Vitamin D deficiency causes gonadal insufficiency, which is important to maintain normal reproductive physiology. More studied are needed to clarify the role of vitamin D in gonadal physiology. Considering the importance of Vitamin D on reproductive functions, its role in causing Oxidative stress and gonadal dysfunction, we suggest randomized control trials in pre-pubertal phase. Continuous....

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