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Article ; Online: Vitamin D-Mediated Regulation of Intestinal Calcium Absorption.

Fleet, James C

2022 Volume 14, Issue 16

Abstract: Vitamin D is a critical regulator of calcium and bone homeostasis. While vitamin D has multiple effects on bone and calcium metabolism, the regulation of intestinal calcium (Ca) absorption efficiency is a critical function for vitamin D. This is ... ...

Abstract	Vitamin D is a critical regulator of calcium and bone homeostasis. While vitamin D has multiple effects on bone and calcium metabolism, the regulation of intestinal calcium (Ca) absorption efficiency is a critical function for vitamin D. This is necessary for optimal bone mineralization during growth, the protection of bone in adults, and the prevention of osteoporosis. Intestinal Ca absorption is regulated by 1,25 dihydroxyvitamin D (1,25(OH)
MeSH term(s)	Animals ; Calcium/metabolism ; Calcium, Dietary/metabolism ; Female ; Intestinal Absorption ; Mice ; Pregnancy ; Receptors, Calcitriol/genetics ; Receptors, Calcitriol/metabolism ; Vitamin D/metabolism ; Vitamins
Chemical Substances	Calcium, Dietary ; Receptors, Calcitriol ; Vitamins ; Vitamin D (1406-16-2) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2022-08-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu14163351
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Article: Vitamin D and Gut Health.

Fleet, James C

Advances in experimental medicine and biology

2022 Volume 1390, Page(s) 155–167

Abstract: Vitamin D is a conditionally required nutrient that can either be obtained from skin synthesis following UVB exposure from the diet. Once in the body, it is metabolized to produce the endocrine hormone, 1,25 dihydroxyvitamin D (1,25(OH)2D), that ... ...

Abstract	Vitamin D is a conditionally required nutrient that can either be obtained from skin synthesis following UVB exposure from the diet. Once in the body, it is metabolized to produce the endocrine hormone, 1,25 dihydroxyvitamin D (1,25(OH)2D), that regulates gene expression in target tissues by interacting with a ligand-activated transcription factor, the vitamin D receptor (VDR). The first, and most responsive, vitamin D target tissue is the intestine. The classical intestinal role for vitamin D is the control of calcium metabolism through the regulation of intestinal calcium absorption. However, studies clearly show that other functions of the intestine are regulated by the molecular actions of 1,25(OH)
MeSH term(s)	Calcium/metabolism ; Hormones ; Humans ; Intestines ; Ligands ; Receptors, Calcitriol/genetics ; Receptors, Calcitriol/metabolism ; Transcription Factors ; Vitamin D/metabolism ; Vitamins
Chemical Substances	Hormones ; Ligands ; Receptors, Calcitriol ; Transcription Factors ; Vitamins ; Vitamin D (1406-16-2) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2022-10-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	410187-X
ISSN	0065-2598
ISSN	0065-2598
DOI	10.1007/978-3-031-11836-4_9
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Article: Vitamin D-Mediated Regulation of Intestinal Calcium Absorption

Fleet, James C.

Nutrients. 2022 Aug. 16, v. 14, no. 16

2022

Abstract	Vitamin D is a critical regulator of calcium and bone homeostasis. While vitamin D has multiple effects on bone and calcium metabolism, the regulation of intestinal calcium (Ca) absorption efficiency is a critical function for vitamin D. This is necessary for optimal bone mineralization during growth, the protection of bone in adults, and the prevention of osteoporosis. Intestinal Ca absorption is regulated by 1,25 dihydroxyvitamin D (1,25(OH)₂ D), a hormone that activates gene transcription following binding to the intestinal vitamin D receptor (VDR). When dietary Ca intake is low, Ca absorption follows a vitamin-D-regulated, saturable pathway, but when dietary Ca intake is high, Ca absorption is predominately through a paracellular diffusion pathway. Deletion of genes that mediate vitamin D action (i.e., VDR) or production (CYP27B1) eliminates basal Ca absorption and prevents the adaptation of mice to low-Ca diets. Various physiologic or disease states modify vitamin-D-regulated intestinal absorption of Ca (enhanced during late pregnancy, reduced due to menopause and aging).
Keywords	absorption ; bone mineralization ; calcium ; homeostasis ; intestinal absorption ; intestines ; menopause ; metabolism ; osteoporosis ; pregnancy ; transcription (genetics) ; vitamin D
Language	English
Dates of publication	2022-0816
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2518386-2
ISSN	2072-6643
ISSN	2072-6643
DOI	10.3390/nu14163351
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Article ; Online: Male Lrp5A214V mice maintain high bone mass during dietary calcium restriction by altering the Vitamin D endocrine system.

Ozgurel, Serra Ucer / Reyes Fernandez, Perla C / Chanpaisaeng, Krittikan / Fleet, James C

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

2024

Abstract: Environmental factors and genetic variation individually impact bone. However, it is not clear how these factors interact to influence peak bone mass accrual. Here we tested whether genetically programmed high bone formation driven by missense mutations ... ...

Abstract	Environmental factors and genetic variation individually impact bone. However, it is not clear how these factors interact to influence peak bone mass accrual. Here we tested whether genetically programmed high bone formation driven by missense mutations in the Lrp5 gene (Lrp5A214V) altered the sensitivity of mice to an environment of inadequate dietary calcium (Ca) intake. Weanling male Lrp5A214V mice and wildtype littermates (control) were fed AIN-93G diets with 0.125%, 0.25%, 0.5% (reference, basal), or 1% Ca from weaning until 12 wks of age (i.e. during bone growth). Urinary Ca, serum Ca, and Ca regulatory hormones (PTH, 1,25 dihydroxyvitamin D3 (1,25(OH)2D3), bone parameters (μCT, ash), and renal/intestinal gene expression were analyzed. As expected, low dietary Ca intake negatively impacted bones and Lrp5A214V mice had higher bone mass and ash content. Although bones of Lrp5A214V mice have more matrix to mineralize, their bones were not more susceptible to low dietary Ca intake. In control mice, low dietary Ca intake exerted expected effects on serum Ca (decreased), PTH (increased), and 1,25(OH)2D3 (increased) as well as their downstream actions (i.e. reducing urinary Ca, increasing markers of intestinal Ca absorption). In contrast, Lrp5A214V mice had elevated serum Ca with a normal PTH response but a blunted 1,25(OH)2D3 response to low dietary Ca that was reflected in the renal 1,25(OH)2D3 producing/degrading enzymes, Cyp27b1 and Cyp24a1. Despite elevated serum Ca in Lrp5A214V mice, urinary Ca was not elevated. Despite an abnormal serum 1,25(OH)2D3 response to low dietary Ca, intestinal markers of Ca absorption (Trpv6, S100g mRNA) were elevated in Lrp5A214V mice and responded to low Ca intake. Collectively, our data indicate that the Lrp5A214V mutation induces changes in Ca homeostasis that permit mice to retain more Ca and support their high bone mass phenotype.
Language	English
Publishing date	2024-01-31
Publishing country	England
Document type	Journal Article
ZDB-ID	632783-7
ISSN	1523-4681 ; 0884-0431
ISSN (online)	1523-4681
ISSN	0884-0431
DOI	10.1093/jbmr/zjae011
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Article ; Online: Intestinal Vitamin D Receptor Is Dispensable for Maintaining Adult Bone Mass in Mice With Adequate Calcium Intake.

Jiang, Heng / Chanpaisaeng, Krittikan / Christakos, Sylvia / Fleet, James C

Endocrinology

2023 Volume 164, Issue 5

Abstract: 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3)-mediated intestinal calcium (Ca) absorption supplies Ca for proper bone mineralization during growth. We tested whether vitamin D receptor (VDR)-mediated 1,25(OH)2D3 signaling is critical for adult Ca absorption and ...

Abstract	1,25-Dihydroxyvitamin D3 (1,25(OH)2D3)-mediated intestinal calcium (Ca) absorption supplies Ca for proper bone mineralization during growth. We tested whether vitamin D receptor (VDR)-mediated 1,25(OH)2D3 signaling is critical for adult Ca absorption and bone by using mice with inducible Vdr gene knockout in the whole intestine (villin-CreERT2+/- × Vdrf/f, WIK) or in the large intestine (Cdx2-CreERT2+/- ×Vdrf/f, LIK). At 4-month-old, Vdr alleles were recombined (0.05 mg tamoxifen/g BW, intraperitoneally [i.p.], 5 days) and mice were fed diets with either 0.5% (adequate) or 0.2% (low) Ca. Ca absorption was examined after 2 weeks while serum 1,25(OH)2D3, bone mass, and bone microarchitecture were examined after 16 weeks. Intestinal and renal gene expression was measured at both time points (n = 12/genotype/diet/time point). On the 0.5% Ca diet, all phenotypes in WIK and LIK mice were similar to the controls. Control mice adapted to the 0.2% low-Ca diet by increasing renal Cyp27b1 mRNA (3-fold), serum 1,25(OH)2D3 level (1.9-fold), and Ca absorption in the duodenum (Dd, + 131%) and proximal colon (PCo, + 28.9%), which prevented bone loss. In WIK mice, low-Ca diet increased serum 1,25(OH)2D3 (4.4-fold) but Ca absorption remained unaltered in the Dd and PCo. Consequently, significant bone loss occurred in WIK mice (e.g., cortical thickness, Ct.Th, -33.7%). LIK mice adapted to the low-Ca diet in the Dd but not the PCo, and the effect on bone phenotypes was milder (e.g., Ct.Th, -13.1%). Our data suggest intestinal VDR in adult mice prevents bone loss under low Ca intake but is dispensable under adequate calcium intake.
MeSH term(s)	Animals ; Mice ; Calcitriol ; Calcium/metabolism ; Intestinal Absorption ; Intestines ; Kidney/metabolism ; Receptors, Calcitriol/genetics ; Receptors, Calcitriol/metabolism ; Vitamin D/metabolism
Chemical Substances	Calcitriol (FXC9231JVH) ; Calcium (SY7Q814VUP) ; Receptors, Calcitriol ; Vitamin D (1406-16-2) ; Vdr protein, mouse
Language	English
Publishing date	2023-03-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	427856-2
ISSN	1945-7170 ; 0013-7227
ISSN (online)	1945-7170
ISSN	0013-7227
DOI	10.1210/endocr/bqad051
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Article ; Online: The role of vitamin D in the endocrinology controlling calcium homeostasis.

Fleet, James C

Molecular and cellular endocrinology

2017 Volume 453, Page(s) 36–45

Abstract: Vitamin D and its' metabolites are a crucial part of the endocrine system that controls whole body calcium homeostasis. The goal of this hormonal control is to regulate serum calcium levels so that they are maintained within a very narrow range. To ... ...

Abstract	Vitamin D and its' metabolites are a crucial part of the endocrine system that controls whole body calcium homeostasis. The goal of this hormonal control is to regulate serum calcium levels so that they are maintained within a very narrow range. To achieve this goal, regulatory events occur in coordination at multiple tissues, e.g. the intestine, kidney, bone, and parathyroid gland. Production of the vitamin D endocrine hormone, 1,25 dihydroxyvitamin D (1,25(OH)
MeSH term(s)	Animals ; Bone and Bones/metabolism ; Calcification, Physiologic ; Calcium/metabolism ; Calcium, Dietary ; Endocrine System/metabolism ; Gene Expression Regulation ; Homeostasis ; Humans ; Intestinal Absorption ; Intestines/metabolism ; Kidney/metabolism ; Mice ; Models, Molecular ; Parathyroid Glands/metabolism ; Receptors, Calcitriol/metabolism ; Vitamin D/metabolism
Chemical Substances	Calcium, Dietary ; Receptors, Calcitriol ; VDR protein, human ; Vitamin D (1406-16-2) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2017-04-09
Publishing country	Ireland
Document type	Journal Article ; Review
ZDB-ID	187438-x
ISSN	1872-8057 ; 0303-7207
ISSN (online)	1872-8057
ISSN	0303-7207
DOI	10.1016/j.mce.2017.04.008
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Article ; Online: Canadian recommendations for vitamin D intake for persons affected by multiple sclerosis.

Atkinson, Stephanie A / Fleet, James C

The Journal of steroid biochemistry and molecular biology

2020 Volume 199, Page(s) 105606

Abstract: In 2016, the Multiple Sclerosis (MS) Society of Canada convened a panel of expert scientists, clinicians and patient advocate to review the evidence for an association between vitamin D status and MS prevention and/or disease modification. The goal was ... ...

Abstract	In 2016, the Multiple Sclerosis (MS) Society of Canada convened a panel of expert scientists, clinicians and patient advocate to review the evidence for an association between vitamin D status and MS prevention and/or disease modification. The goal was to develop clear and accurate recommendations on optimal vitamin D intake and status for people affected by MS for use in clinical practice and public health policy. The final consensus report was based on a review and grading of existing published papers combined with expert opinions of panel members. The report led to recommendations published in November of 2018 on the website of the MS Society of Canada, one in a format for use by health professionals and another in a question and answer format that was targeted to persons affected by MS and the general public. For people at risk of developing MS, the vitamin D recommendations are similar to those for the general public following the Dietary Reference Intakes (DRI) for Canada and the United States. Adults should achieve and maintain a normal vitamin D status with monitoring by physicians (serum 25-hydroxyvitamin D (25(OH)D) = 50-125 nmol/L, requiring 600-4000 IU vitamin D/d intake). For pregnant women, newborn infants, and all youth at risk of MS, vitamin D intakes should also follow DRI recommendations but additionally their serum 25-(OH)D should be monitored. For persons living with MS, existing evidence did not allow prediction of a vitamin D intake that might modify MS disease course. For this group the recommendations included: (1) serum 25-(OH)D should be maintained in the range of 50-125 nmol/L (600-4000 IU/d intake).; and (2) vitamin D should not be used as a standalone treatment for MS. For children and adolescents, serum 25OHD status was recommended to be measured upon diagnosis of a first clinical demyelinating event, and monitored every 6 months to achieve a target of 75 nmol/L Since people living with MS are at increased risk of osteoporosis, falls, and bone fractures, it was recommended to achieve a minimum serum 25OHD concentration that is protective for bone health in the general population. The revision of the MS Society recommendations on vitamin D awaits future clinical trial evidence.
MeSH term(s)	Adult ; Bone Density/drug effects ; Calcifediol/adverse effects ; Calcifediol/therapeutic use ; Canada/epidemiology ; Child ; Dietary Supplements ; Female ; Fractures, Bone/diet therapy ; Fractures, Bone/metabolism ; Fractures, Bone/pathology ; Humans ; Infant ; Infant, Newborn ; Multiple Sclerosis/blood ; Multiple Sclerosis/diet therapy ; Multiple Sclerosis/metabolism ; Multiple Sclerosis/pathology ; Nutritional Status ; Osteoporosis/diet therapy ; Osteoporosis/metabolism ; Pregnancy ; Vitamin D/adverse effects ; Vitamin D/analogs & derivatives ; Vitamin D/blood ; Vitamin D/therapeutic use ; Vitamin D Deficiency/diet therapy ; Vitamin D Deficiency/metabolism ; Vitamin D Deficiency/pathology
Chemical Substances	Vitamin D (1406-16-2) ; 25-hydroxyvitamin D (A288AR3C9H) ; Calcifediol (P6YZ13C99Q)
Language	English
Publishing date	2020-01-22
Publishing country	England
Document type	Journal Article
ZDB-ID	1049188-0
ISSN	1879-1220 ; 0960-0760
ISSN (online)	1879-1220
ISSN	0960-0760
DOI	10.1016/j.jsbmb.2020.105606
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Article ; Online: Diet X Gene Interactions Control Femoral Bone Adaptation to Low Dietary Calcium.

Chanpaisaeng, Krittikan / Reyes-Fernandez, Perla C / Dilkes, Brian / Fleet, James C

JBMR plus

2022 Volume 6, Issue 9, Page(s) e10668

Abstract: Genetics and dietary calcium (Ca) are each critical regulators of peak bone mass but it is unclear how genetics alters the physiologic response of bone to dietary Ca restriction (RCR). Here, we conducted genetic mapping in C57BL/6J × DBA/2J (BXD) ... ...

Abstract	Genetics and dietary calcium (Ca) are each critical regulators of peak bone mass but it is unclear how genetics alters the physiologic response of bone to dietary Ca restriction (RCR). Here, we conducted genetic mapping in C57BL/6J × DBA/2J (BXD) recombinant inbred mouse lines to identify environmentally sensitive loci controlling whole-bone mass (bone mineral density [BMD], bone mineral content [BMC]), distal trabecular bone, and cortical bone midshaft of the femur. Mice were fed adequate (basal) or low Ca diets from 4-12 weeks of age. Femurs were then examined by dual-energy X-ray absorptiometry (DXA) and micro-computed tomography (μCT). Body size-corrected residuals were used for statistical analysis, genetic mapping, and to estimate narrow sense heritability (h
Language	English
Publishing date	2022-08-19
Publishing country	England
Document type	Journal Article
ISSN	2473-4039
ISSN (online)	2473-4039
DOI	10.1002/jbm4.10668
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Article ; Online: Animal models of gastrointestinal and liver diseases. New mouse models for studying dietary prevention of colorectal cancer.

Fleet, James C

American journal of physiology. Gastrointestinal and liver physiology

2014 Volume 307, Issue 3, Page(s) G249–59

Abstract: Colorectal cancer is a heterogeneous disease that is one of the major causes of cancer death in the U.S. There is evidence that lifestyle factors like diet can modulate the course of this disease. Demonstrating the benefit and mechanism of action of ... ...

Abstract	Colorectal cancer is a heterogeneous disease that is one of the major causes of cancer death in the U.S. There is evidence that lifestyle factors like diet can modulate the course of this disease. Demonstrating the benefit and mechanism of action of dietary interventions against colon cancer will require studies in preclinical models. Many mouse models have been developed to study colon cancer but no single model can reflect all types of colon cancer in terms of molecular etiology. In addition, many models develop only low-grade cancers and are confounded by development of the disease outside of the colon. This review will discuss how mice can be used to model human colon cancer and it will describe a variety of new mouse models that develop colon-restricted cancer as well as more advanced phenotypes for studies of late-state disease.
MeSH term(s)	Animals ; Chemoprevention/methods ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/prevention & control ; Diet/adverse effects ; Disease Models, Animal ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Humans ; Mice ; Mice, Mutant Strains ; Mice, Transgenic ; Mutation ; Phenotype ; Risk Reduction Behavior ; Species Specificity
Language	English
Publishing date	2014-05-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	603840-2
ISSN	1522-1547 ; 0193-1857
ISSN (online)	1522-1547
ISSN	0193-1857
DOI	10.1152/ajpgi.00019.2014
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Article ; Online: Intestinal responses to 1,25 dihydroxyvitamin D are not improved by higher intestinal VDR levels resulting from intestine-specific transgenic expression of VDR in mice.

Fleet, James C / Reyes-Fernandez, Perla

The Journal of steroid biochemistry and molecular biology

2020 Volume 200, Page(s) 105670

Abstract: Intestinal calcium (Ca) absorption depends upon vitamin D signaling through the vitamin D receptor (VDR) in the proximal and distal intestine while lower VDR content causes intestinal resistance to 1,25 dihydroxyvitamin D (1,25(OH) ...

Abstract	Intestinal calcium (Ca) absorption depends upon vitamin D signaling through the vitamin D receptor (VDR) in the proximal and distal intestine while lower VDR content causes intestinal resistance to 1,25 dihydroxyvitamin D (1,25(OH)
MeSH term(s)	Animals ; Calcitriol/pharmacology ; Calcium/metabolism ; Calcium/urine ; Femur/diagnostic imaging ; Intestinal Absorption/drug effects ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/metabolism ; Male ; Mice, Inbred C57BL ; Mice, Transgenic ; Receptors, Calcitriol/genetics ; Receptors, Calcitriol/metabolism ; Vitamins/pharmacology
Chemical Substances	Receptors, Calcitriol ; Vitamins ; Calcitriol (FXC9231JVH) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2020-04-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1049188-0
ISSN	1879-1220 ; 0960-0760
ISSN (online)	1879-1220
ISSN	0960-0760
DOI	10.1016/j.jsbmb.2020.105670
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