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  1. Article ; Online: Vitamin D binding protein gene polymorphisms are associated with lower plasma 25-hydroxy-cholecalciferol concentrations in Ethiopian lactating women.

    Hart, Matthew D / Girma, Meron / Strong, Morgan D / Tadesse, Birkneh Tilahun / Taddesse, Biruk Mulugeta / Alemayehu, Fikadu Reta / Stoecker, Barbara J / Chowanadisai, Winyoo

    Nutrition research (New York, N.Y.)

    2022  Volume 107, Page(s) 86–95

    Abstract: Ethiopian women have been reported to have low plasma 25-hydroxy-cholecalciferol (25(OH)D) concentrations despite an abundance of sunshine. Low dietary vitamin D intake, limited skin exposure to sun, and genetics are among factors suggested to affect ... ...

    Abstract Ethiopian women have been reported to have low plasma 25-hydroxy-cholecalciferol (25(OH)D) concentrations despite an abundance of sunshine. Low dietary vitamin D intake, limited skin exposure to sun, and genetics are among factors suggested to affect vitamin D status in this population. In this study (Clinical Trial NCT02210884), we hypothesized that polymorphisms in the vitamin D binding protein (VDBP) gene (rs7041, rs4588) are associated with reduced plasma 25(OH)D concentrations in Ethiopian women. Lactating Ethiopian women (n = 110) were randomly assigned to weekly administration of vitamin D3 (15,000 IU) or a placebo. Plasma 25(OH)D was measured at baseline (within 2 weeks of delivery, before supplementation) and at 3, 6, and 12 months after delivery. Associations between VDBP polymorphism status for rs7041 and rs4588 and plasma 25(OH)D were determined by analysis of variance and multiple linear and logistic regressions. Multiple linear regression with maternal age as a covariate revealed that rs7041 is associated with reduced plasma 25(OH)D (P = .021) and more risk alleles at rs7041 and rs4588 are associated with reduced plasma 25(OH)D (P = .017). Logistic regression models for vitamin D insufficiency showed that additional risk alleles for rs7041 and rs4588 are associated with increased odds ratios (OR = 1.66; 95% CI, 1.10-2.62; P = .019) for plasma 25(OH)D below 40 nmol/L. Supplementation increased plasma 25(OH)D at 3 months in women with fewer risk alleles and across all genotypes at 6 and 12 months. VDBP polymorphisms may contribute to vitamin D insufficiency in Ethiopian lactating women. Furthermore, VDBP polymorphisms may blunt short-term responses to vitamin D supplementation and require longer periods of intervention.
    MeSH term(s) Female ; Humans ; Calcifediol/blood ; Cholecalciferol ; Ethiopia ; Lactation ; Polymorphism, Single Nucleotide ; Vitamin D ; Vitamin D Deficiency ; Vitamin D-Binding Protein/genetics
    Chemical Substances Calcifediol (P6YZ13C99Q) ; Cholecalciferol (1C6V77QF41) ; Vitamin D (1406-16-2) ; Vitamin D-Binding Protein ; GC protein, human
    Language English
    Publishing date 2022-09-14
    Publishing country United States
    Document type Randomized Controlled Trial ; Journal Article
    ZDB-ID 582432-1
    ISSN 1879-0739 ; 0271-5317
    ISSN (online) 1879-0739
    ISSN 0271-5317
    DOI 10.1016/j.nutres.2022.09.003
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  2. Article: Vitamin D Binding Protein Gene Polymorphisms Are Associated with Lower Plasma 25-Hydroxy-Cholecalciferol Concentrations in Ethiopian Lactating Women

    Hart, Matthew D. / Girma, Meron / Strong, Morgan D. / Tadesse, Birkneh Tilahun / Taddesse, Biruk Mulugeta / Alemayehu, Fikadu Reta / Stoecker, Barbara J. / Chowanadisai, Winyoo

    Nutrition research. 2022 Sept. 03,

    2022  

    Abstract: Ethiopian women have been reported to have low plasma 25-hydroxy- cholecalciferol (25(OH)D) concentrations despite an abundance of sunshine. Low dietary vitamin D intake, limited skin exposure to sun, and genetics are among factors suggested to affect ... ...

    Abstract Ethiopian women have been reported to have low plasma 25-hydroxy- cholecalciferol (25(OH)D) concentrations despite an abundance of sunshine. Low dietary vitamin D intake, limited skin exposure to sun, and genetics are among factors suggested to affect vitamin D status in this population. In this study (Clinical Trial NCT02210884), we hypothesized that polymorphisms in the vitamin D binding protein (VDBP) gene (rs7041, rs4588) are associated with reduced plasma 25(OH)D concentrations in Ethiopian women. Lactating Ethiopian women (n=110) were randomly assigned to weekly administration of vitamin D3 (15,000 IUs) or a placebo. Plasma 25(OH)D was measured at baseline (within 2 weeks of delivery, before supplementation) and at 3, 6, and 12 months after delivery. Associations between VDBP polymorphism status for rs7041 and rs4588 and plasma 25(OH)D were determined by ANOVA and multiple linear and logistic regressions. Multiple linear regression with maternal age as a covariate revealed that rs7041 is associated with reduced plasma 25(OH)D (p=0.021) and more risk alleles at rs7041 and rs4588 are associated with reduced plasma 25(OH)D (p=0.017). Logistic regression models for vitamin D insufficiency showed that additional risk alleles for rs7041 and rs4588 are associated with increased odds ratios (OR=1.66, 95% CI 1.10-2.62, p=0.019) for plasma 25(OH)D below 40 nmol/L. Supplementation increased plasma 25(OH)D at 3 months in women with fewer risk alleles and across all genotypes at 6 and 12 months. VDBP polymorphisms may contribute to vitamin D insufficiency in Ethiopian lactating women. Furthermore, VDBP polymorphisms may blunt short-term responses to vitamin D supplementation and require longer periods of intervention.
    Keywords cholecalciferol ; clinical trials ; dermal exposure ; genes ; nutrition research ; placebos ; regression analysis ; risk ; solar radiation
    Language English
    Dates of publication 2022-0903
    Publishing place Elsevier Inc.
    Document type Article
    Note Pre-press version
    ZDB-ID 582432-1
    ISSN 1879-0739 ; 0271-5317
    ISSN (online) 1879-0739
    ISSN 0271-5317
    DOI 10.1016/j.nutres.2022.09.003
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  3. Article ; Online: Genetic and Genomic Advances in Developmental Models: Applications for Nutrition Research.

    Chowanadisai, Winyoo / Hart, Matthew D / Strong, Morgan D / Graham, David M / Rucker, Robert B / Smith, Brenda J / Keen, Carl L / Messerli, Mark A

    Advances in nutrition (Bethesda, Md.)

    2020  Volume 11, Issue 4, Page(s) 971–978

    Abstract: There is increasing appreciation that dietary components influence and interact with genes important to metabolism. How such influences impact developmental regulation and programming or risks of chronic diseases remains unclear. Nutrition is recognized ... ...

    Abstract There is increasing appreciation that dietary components influence and interact with genes important to metabolism. How such influences impact developmental regulation and programming or risks of chronic diseases remains unclear. Nutrition is recognized to affect development and chronic diseases, but our understanding about how genes essential to nutrient metabolism regulate development and impact risks of these diseases remains unclear. Historically, mammalian models, especially rodents such as rats and mice, have been the primary models used for nutrition and developmental nutrition science, although their complexity and relatively slow rate of development often compromise rapid progress in resolving fundamental, genetic-related questions. Accordingly, the objective of this review is to highlight the opportunities for developmental models in the context of uncovering the function of gene products that are relevant to human nutrition and provide the scientific bases for these opportunities. We present recent studies in zebrafish related to obesity as applications of developmental models in nutritional science. Although the control of external factors and dependent variables, such as nutrition, can be a challenge, suggestions for standardizations related to diet are made to improve consistency in findings between laboratories. The review also highlights the need for standardized diets across different developmental models, which could improve consistency in findings across laboratories. Alternative and developmental animal models have advantages and largely untapped potential for the advancement of nutrigenomics and nutritionally relevant research areas.
    MeSH term(s) Animals ; Diet ; Genomics ; Humans ; Mice ; Nutrigenomics ; Nutritional Status ; Rats ; Zebrafish
    Language English
    Publishing date 2020-03-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2583634-1
    ISSN 2156-5376 ; 2156-5376
    ISSN (online) 2156-5376
    ISSN 2156-5376
    DOI 10.1093/advances/nmaa022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: A role for zinc transporter gene SLC39A12 in the nervous system and beyond.

    Davis, Danielle N / Strong, Morgan D / Chambers, Emily / Hart, Matthew D / Bettaieb, Ahmed / Clarke, Stephen L / Smith, Brenda J / Stoecker, Barbara J / Lucas, Edralin A / Lin, Dingbo / Chowanadisai, Winyoo

    Gene

    2021  Volume 799, Page(s) 145824

    Abstract: The SLC39A12 gene encodes the zinc transporter protein ZIP12, which is expressed across many tissues and is highly abundant in the vertebrate nervous system. As a zinc transporter, ZIP12 functions to transport zinc across cellular membranes, including ... ...

    Abstract The SLC39A12 gene encodes the zinc transporter protein ZIP12, which is expressed across many tissues and is highly abundant in the vertebrate nervous system. As a zinc transporter, ZIP12 functions to transport zinc across cellular membranes, including cellular zinc influx across the plasma membrane. Genome-wide association and exome sequencing studies have shown that brain susceptibility-weighted magnetic resonance imaging (MRI) intensity is associated with ZIP12 polymorphisms and rare mutations. ZIP12 is required for neural tube closure and embryonic development in Xenopus tropicalis. Frog embryos depleted of ZIP12 by antisense morpholinos develop an anterior neural tube defect and lack viability. ZIP12 is also necessary for neurite outgrowth and mitochondrial function in mouse neural cells. ZIP12 mRNA is increased in brain regions of schizophrenic patients. Outside of the nervous system, hypoxia induces ZIP12 expression in multiple mammalian species, including humans, which leads to endothelial and smooth muscle thickening in the lung and contributes towards pulmonary hypertension. Other studies have associated ZIP12 with other diseases such as cancer. Given that ZIP12 is highly expressed in the brain and that susceptibility-weighted MRI is associated with brain metal content, ZIP12 may affect neurological diseases and psychiatric illnesses such as Parkinson's disease, Alzheimer's disease, and schizophrenia. Furthermore, the induction of ZIP12 and resultant zinc uptake under pathophysiological conditions may be a critical component of disease pathology, such as in pulmonary hypertension. Drug compounds that bind metals like zinc may be able to treat diseases associated with impaired zinc homeostasis and altered ZIP12 function.
    MeSH term(s) Animals ; Autistic Disorder/metabolism ; Biological Specimen Banks ; Cation Transport Proteins/physiology ; Gene Expression Regulation, Developmental ; Humans ; Lung/physiopathology ; Multigene Family ; Nervous System Physiological Phenomena ; Neurodegenerative Diseases/etiology ; Oxidative Stress/physiology ; United Kingdom ; Vertebrates/genetics ; Xenopus Proteins/physiology ; Zinc/metabolism
    Chemical Substances Cation Transport Proteins ; SLC39A12 protein, human ; Xenopus Proteins ; slc39a12 protein, Xenopus ; Zinc (J41CSQ7QDS)
    Language English
    Publishing date 2021-07-09
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 391792-7
    ISSN 1879-0038 ; 0378-1119
    ISSN (online) 1879-0038
    ISSN 0378-1119
    DOI 10.1016/j.gene.2021.145824
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  5. Article: A role for zinc transporter gene SLC39A12 in the nervous system and beyond

    Davis, Danielle N. / Strong, Morgan D. / Chambers, Emily / Hart, Matthew D. / Bettaieb, Ahmed / Clarke, Stephen L. / Smith, Brenda J. / Stoecker, Barbara J. / Lucas, Edralin A. / Lin, Dingbo / Chowanadisai, Winyoo

    Gene. 2021 Oct. 05, v. 799

    2021  

    Abstract: The SLC39A12 gene encodes the zinc transporter protein ZIP12, which is expressed across many tissues and is highly abundant in the vertebrate nervous system. As a zinc transporter, ZIP12 functions to transport zinc across cellular membranes, including ... ...

    Abstract The SLC39A12 gene encodes the zinc transporter protein ZIP12, which is expressed across many tissues and is highly abundant in the vertebrate nervous system. As a zinc transporter, ZIP12 functions to transport zinc across cellular membranes, including cellular zinc influx across the plasma membrane. Genome-wide association and exome sequencing studies have shown that brain susceptibility-weighted magnetic resonance imaging (MRI) intensity is associated with ZIP12 polymorphisms and rare mutations. ZIP12 is required for neural tube closure and embryonic development in Xenopus tropicalis. Frog embryos depleted of ZIP12 by antisense morpholinos develop an anterior neural tube defect and lack viability. ZIP12 is also necessary for neurite outgrowth and mitochondrial function in mouse neural cells. ZIP12 mRNA is increased in brain regions of schizophrenic patients. Outside of the nervous system, hypoxia induces ZIP12 expression in multiple mammalian species, including humans, which leads to endothelial and smooth muscle thickening in the lung and contributes towards pulmonary hypertension. Other studies have associated ZIP12 with other diseases such as cancer. Given that ZIP12 is highly expressed in the brain and that susceptibility-weighted MRI is associated with brain metal content, ZIP12 may affect neurological diseases and psychiatric illnesses such as Parkinson’s disease, Alzheimer’s disease, and schizophrenia. Furthermore, the induction of ZIP12 and resultant zinc uptake under pathophysiological conditions may be a critical component of disease pathology, such as in pulmonary hypertension. Drug compounds that bind metals like zinc may be able to treat diseases associated with impaired zinc homeostasis and altered ZIP12 function.
    Keywords Xenopus tropicalis ; brain ; drugs ; embryogenesis ; frogs ; genes ; homeostasis ; hypertension ; hypoxia ; lungs ; magnetism ; mice ; mitochondria ; neural tube defects ; neurites ; plasma membrane ; schizophrenia ; smooth muscle ; transport proteins ; viability ; zinc
    Language English
    Dates of publication 2021-1005
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 391792-7
    ISSN 1879-0038 ; 0378-1119
    ISSN (online) 1879-0038
    ISSN 0378-1119
    DOI 10.1016/j.gene.2021.145824
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  6. Article ; Online: Role of zinc transporter ZIP12 in susceptibility-weighted brain magnetic resonance imaging (MRI) phenotypes and mitochondrial function.

    Strong, Morgan D / Hart, Matthew D / Tang, Tony Z / Ojo, Babajide A / Wu, Lei / Nacke, Mariah R / Agidew, Workneh T / Hwang, Hong J / Hoyt, Peter R / Bettaieb, Ahmed / Clarke, Stephen L / Smith, Brenda J / Stoecker, Barbara J / Lucas, Edralin A / Lin, Dingbo / Chowanadisai, Winyoo

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology

    2020  Volume 34, Issue 9, Page(s) 10702–12725

    Abstract: Brain zinc dysregulation is linked to many neurological disorders. However, the mechanisms regulating brain zinc homeostasis are poorly understood. We performed secondary analyses of brain MRI GWAS and exome sequencing data from adults in the UK Biobank. ...

    Abstract Brain zinc dysregulation is linked to many neurological disorders. However, the mechanisms regulating brain zinc homeostasis are poorly understood. We performed secondary analyses of brain MRI GWAS and exome sequencing data from adults in the UK Biobank. Coding ZIP12 polymorphisms in zinc transporter ZIP12 (SLC39A12) were associated with altered brain susceptibility weighted MRI (swMRI). Conditional and joint association analyses revealed independent GWAS signals in linkage disequilibrium with 2 missense ZIP12 polymorphisms, rs10764176 and rs72778328, with reduced zinc transport activity. ZIP12 rare coding variants predicted to be deleterious were associated with similar impacts on brain swMRI. In Neuro-2a cells, ZIP12 deficiency by short hairpin RNA (shRNA) depletion or CRISPR/Cas9 genome editing resulted in impaired mitochondrial function, increased superoxide presence, and detectable protein carbonylation. Inhibition of Complexes I and IV of the electron transport chain reduced neurite outgrowth in ZIP12 deficient cells. Transcriptional coactivator PGC-1α, mitochondrial superoxide dismutase (SOD2), and chemical antioxidants α-tocopherol, MitoTEMPO, and MitoQ restored neurite extension impaired by ZIP12 deficiency. Mutant forms of α-synuclein and tau linked to familial Parkinson's disease and frontotemporal dementia, respectively, reduced neurite outgrowth in cells deficient in ZIP12. Zinc and ZIP12 may confer resilience against neurological diseases or premature aging of the brain.
    MeSH term(s) Animals ; Brain/diagnostic imaging ; Brain/metabolism ; CHO Cells ; Cation Transport Proteins/deficiency ; Cation Transport Proteins/genetics ; Cation Transport Proteins/metabolism ; Cell Line, Tumor ; Cricetinae ; Cricetulus ; Humans ; Magnetic Resonance Imaging/methods ; Mice ; Mitochondria/genetics ; Mitochondria/metabolism ; Neuronal Outgrowth/genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism ; Polymorphism, Single Nucleotide ; RNA Interference ; Superoxide Dismutase/genetics ; Superoxide Dismutase/metabolism ; Zinc/metabolism
    Chemical Substances Cation Transport Proteins ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; SLC39A12 protein, human ; Superoxide Dismutase (EC 1.15.1.1) ; superoxide dismutase 2 (EC 1.15.1.1) ; Zinc (J41CSQ7QDS)
    Language English
    Publishing date 2020-07-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    DOI 10.1096/fj.202000772R
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  7. Article ; Online: Pinto beans modulate the gut microbiome, augment MHC II protein, and antimicrobial peptide gene expression in mice fed a normal or western-style diet.

    Ojo, Babajide A / Lu, Peiran / Alake, Sanmi E / Keirns, Bryant / Anderson, Kendall / Gallucci, Grace / Hart, Matthew D / El-Rassi, Guadalupe Davila / Ritchey, Jerry W / Chowanadisai, Winyoo / Lin, Dingbo / Clarke, Stephen / Smith, Brenda J / Lucas, Edralin A

    The Journal of nutritional biochemistry

    2020  Volume 88, Page(s) 108543

    Abstract: The onset of type 2 diabetes in obesity is associated with gut dysbiosis and a failure to confine commensal bacteria and toxins to the gut lumen while prebiotics may prevent these effects. This study evaluated the effects of pinto beans (PB) ... ...

    Abstract The onset of type 2 diabetes in obesity is associated with gut dysbiosis and a failure to confine commensal bacteria and toxins to the gut lumen while prebiotics may prevent these effects. This study evaluated the effects of pinto beans (PB) supplementation on cecal bacteria, short-chain fatty acids (SCFAs), distal ileal antigen presentation marker (major histocompatibility complex [MHC] II) and antimicrobial peptide genes during short-term high-fat, high sucrose (HFS) feeding. Six-week-old, male C57BL/6J mice were randomly assigned to four groups (n=12/group), and fed a control (C) or HFS diet with or without cooked PB (10%, wt/wt) for 30 days. Supplemental PB in both the C and HFS diets decreased the abundance of Tenericutes and the sulfate-reducing bacteria Bilophila. In contrast, PB raised the abundance of taxa within the SCFAs-producing family, Lachnospiraceae, compared to groups without PB. Consequently, fecal butyric acid was significantly higher in PB-supplemented groups compared to C and HFS groups. PB reversed the HFS-induced ablation of the distal ileal STAT3 phosphorylation, and up-regulated antimicrobial peptide genes (Reg3γ and Reg3β). Furthermore, the expression of MHC II protein was elevated in the PB supplemented groups compared to C and HFS. Tenericutes and Bilophilia negatively correlated with activated STAT3 and MHC II proteins. Finally, supplemental PB improved fasting blood glucose, glucose tolerance and suppressed TNFα and inducible nitric oxide synthase mRNA in the visceral adipose tissue. Put together, the beneficial impact of PB supplementation on the gut may be central to its potential to protect against diet-induced inflammation and impaired glucose tolerance.
    MeSH term(s) Animals ; Cecum/metabolism ; Diet, Western ; Dietary Supplements ; Dysbiosis/diet therapy ; Dysbiosis/metabolism ; Fatty Acids, Volatile/metabolism ; Feces/microbiology ; Gastrointestinal Microbiome ; Gene Expression ; Genes, MHC Class II ; Humans ; Intra-Abdominal Fat/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/metabolism ; Phaseolus ; Pore Forming Cytotoxic Proteins/genetics ; Pore Forming Cytotoxic Proteins/metabolism
    Chemical Substances Fatty Acids, Volatile ; Pore Forming Cytotoxic Proteins
    Language English
    Publishing date 2020-11-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1014929-6
    ISSN 1873-4847 ; 0955-2863
    ISSN (online) 1873-4847
    ISSN 0955-2863
    DOI 10.1016/j.jnutbio.2020.108543
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