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Micronutrients in Metabolic Health

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 19412

Special Issue Editor

School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, UK
Interests: nutriepigenomics; micronutrients
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Obesity and type 2 diabetes (T2D) are a major public health problem. Genome-wide association studies only explain a small fraction of the heritability of these disorders (less than 2% for obesity and 5–10% for T2D). These low heritability estimates suggest that lifestyle factors via epigenetic mechanisms could explain the missing heritability and play a key role in these diseases. Nutritional imbalances, either macro- or micro-nutrient intake during the prenatal or postnatal life, could lead to epigenetic reprogramming which is associated to increased obesity, T2D, gestational diabetes, and cardiovascular disease. More importantly, recent studies in micronutrient deficiency during pregnancy have been shown to induce distinctive changes in the epigenome and increase metabolic risk. By contrast, sufficient nutrient intake has shown improved epigenetic marks and mitigated disease risk. However, the mechanistic understanding of these micronutrients in metabolic diseases is still limited, which can regulate a large collection of coding and noncoding transcripts involved in metabolic pathways. Hence, the goal of this Special Issue is to broaden the molecular understanding on the role of micronutrients and epigenetic mechanisms, which will uncover strategies to target epigenetic plasticity which may, in the future, offer novel and realistic opportunities to prevent and treat obesity and related disorders. We invite authors to submit their original research as well as review articles describing basic and translational findings with a special focus on “Micronutrients in Metabolic Health”.

Dr. Adaikala Antonysunil
Guest Editor

Manuscript Submission Information

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Keywords

  • micronutrients
  • vitamin B12
  • vitamin D
  • epigenetics
  • obesity
  • type 2 diabetes
  • gestational diabetes
  • insulin resistance
  • cardiovasular disease
  • maternal and fetal programming

Published Papers (5 papers)

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Research

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11 pages, 927 KiB  
Article
Impairment of Vitamin D Nutritional Status and Metabolic Profile Are Associated with Worsening of Obesity According to the Edmonton Obesity Staging System
by Adryana Cordeiro, Mariana Luna, Silvia Elaine Pereira, Carlos José Saboya and Andrea Ramalho
Int. J. Mol. Sci. 2022, 23(23), 14705; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232314705 - 25 Nov 2022
Cited by 2 | Viewed by 1215
Abstract
Obesity is associated with a higher risk of Vitamin D (VD) inadequacy and metabolic diseases. The Edmonton Obesity Staging System (EOSS) is an innovative tool for the evaluation of obesity that goes beyond body weight and considers clinic, functional and menta- health issues. [...] Read more.
Obesity is associated with a higher risk of Vitamin D (VD) inadequacy and metabolic diseases. The Edmonton Obesity Staging System (EOSS) is an innovative tool for the evaluation of obesity that goes beyond body weight and considers clinic, functional and menta- health issues. This study aimed to evaluate the nutritional status of VD according to the stages of EOSS and its relationship with the metabolic profile. In the cross-sectional study, we evaluated anthropometric parameters, physical activity, blood pressure, biochemical and metabolic variables, and VD nutritional status. A total of 226 individuals were categorized using EOSS: 1.3%, 22.1%, 62.9%, and 13.7% were in stages 0, 1, 2 and 3, respectively. Regarding the metabolic changes and comorbidities, insulin resistance and hyperuricemia were diagnosed in some individuals in EOSS 1, 2, and 3. EOSS 2 and 3 presented a significant relative-risk for the development of arterial hypertension, metabolic syndrome, and liver disease, compared with EOSS 0. In all stages, there were observed means of 25(OH)D serum concentrations below 30 ng/mL (EOSS 0 24.9 ± 3.3 ng/mL; EOSS 3 15.9 ± 5.4 ng/mL; p = 0.031), and 25(OH)D deficiency was present in all stages. Individuals with obesity classified in more advanced stages of EOSS had lower serum concentrations of 25(OH)D and a worse metabolic profile. Full article
(This article belongs to the Special Issue Micronutrients in Metabolic Health)
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26 pages, 6365 KiB  
Article
Nature-Inspired Effects of Naturally Occurring Trace Element-Doped Hydroxyapatite Combined with Surface Interactions of Mineral-Apatite Single Crystals on Human Fibroblast Behavior
by Malgorzata Tyszka-Czochara, Marzena Suder, Agnieszka Dołhańczuk-Śródka, Małgorzata Rajfur, Katarzyna Grata, Michał Starosta, Agnieszka Jagoda-Pasternak, Wiktor Kasprzyk, Anna K. Nowak, Saeid Ahmadzadeh, Dorota Kopeć, Piotr Suryło, Tomasz Świergosz and Katarzyna M. Stadnicka
Int. J. Mol. Sci. 2022, 23(2), 802; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23020802 - 12 Jan 2022
Cited by 4 | Viewed by 1965
Abstract
Innovative engineering design for biologically active hydroxyapatites requires enhancing both mechanical and physical properties, along with biocompatibility, by doping with appropriate chemical elements. Herein, the purpose of this investigation was to evaluate and elucidate the model of naturally occurring hydroxyapatite and the effects [...] Read more.
Innovative engineering design for biologically active hydroxyapatites requires enhancing both mechanical and physical properties, along with biocompatibility, by doping with appropriate chemical elements. Herein, the purpose of this investigation was to evaluate and elucidate the model of naturally occurring hydroxyapatite and the effects of doped trace elements on the function of normal human fibroblasts, representing the main cells of connective tissues. The substrates applied (geological apatites with hexagonal prismatic crystal habit originated from Slyudyanka, Lake Baikal, Russia (GAp) and from Imilchil, The Atlas Mountains, Morocco (YAp)) were prepared from mineral natural apatite with a chemical composition consistent with the building blocks of enamel and enriched with a significant F content. Materials in the form of powders, extracts and single-crystal plates have been investigated. Moreover, the effects on the function of fibroblasts cultured on the analyzed surfaces in the form of changes in metabolic activity, proliferation and cell morphology were evaluated. Apatite plates were also evaluated for cytotoxicity and immune cell activation capacity. The results suggest that a moderate amount of F has a positive effect on cell proliferation, whereas an inhibitory effect was attributed to the Cl concentration. It was found that for (100) GAp plate, fibroblast proliferation was significantly increased, whereas for (001) YAp plate, it was significantly reduced, with no cytotoxic effect and no immune response from macrophages exposed to these materials. The study of the interaction of fibroblasts with apatite crystal surfaces provides a characterization relevant to medical applications and may contribute to the design of biomaterials suitable for medical applications and the evaluation of their bioavailability. Full article
(This article belongs to the Special Issue Micronutrients in Metabolic Health)
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10 pages, 1291 KiB  
Article
Intracellular and Tissue Levels of Vitamin B12 in Hepatocytes Are Modulated by CD320 Receptor and TCN2 Transporter
by Joseph Boachie, Antonysunil Adaikalakoteswari, Ilona Goljan, Jinous Samavat, Felino R. Cagampang and Ponnusamy Saravanan
Int. J. Mol. Sci. 2021, 22(6), 3089; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063089 - 17 Mar 2021
Cited by 10 | Viewed by 2709
Abstract
The liver mass constitutes hepatocytes expressing receptors for vitamin B12 (B12)-bound transporters in circulation. However, intrahepatic and circulating B12 interrelationship levels remain unclear. We assessed the intracellular B12 levels at various circulating B12 concentrations in human HepG2 cell-line and liver tissue levels of [...] Read more.
The liver mass constitutes hepatocytes expressing receptors for vitamin B12 (B12)-bound transporters in circulation. However, intrahepatic and circulating B12 interrelationship levels remain unclear. We assessed the intracellular B12 levels at various circulating B12 concentrations in human HepG2 cell-line and liver tissue levels of B12 in the C57BL/6 mouse model. In HepG2 cells treated with a range of B12 concentrations, the intracellular and circulatory B12 levels, transcript and protein levels of B12 receptor (CD320) and transporter (TCN2) were determined using immunoassays, qRT-PCR and Western blot, respectively. Similar assessments were done in plasma and liver tissue of C57BL/6 mice, previously fed a diet of either a high or low B12 (30.82 µg B12/kg and 7.49 µg B12/kg, respectively) for 8–10 weeks. The physiological B12 status (0.15–1 nM) resulted in increased levels of intracellular B12 in HepG2 cells compared to supraphysiological levels of B12 (>1 nM). Gene and protein expression of CD320 and TCN2 were also higher at physiological levels of B12. Progressively increasing extracellular B12 to supraphysiological levels led to relative decreased levels of intracellular B12, lower expression of gene and protein levels of CD320 and TCN2. Similar results were observed in liver tissue from mice fed on a low B12 diet verses high B12 diet. These findings suggest that unlike supraphysiological B12, physiological levels of B12 in the extracellular media or circulation accelerates active transport of B12, and expression of CD320 and TCN2, resulting in higher relative uptake of B12 in hepatocytes. Full article
(This article belongs to the Special Issue Micronutrients in Metabolic Health)
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22 pages, 9749 KiB  
Article
Interspecific Variation in One-Carbon Metabolism within the Ovarian Follicle, Oocyte, and Preimplantation Embryo: Consequences for Epigenetic Programming of DNA Methylation
by Constance E. Clare, Valerie Pestinger, Wing Yee Kwong, Desmond A. R. Tutt, Juan Xu, Helen M. Byrne, David A. Barrett, Richard D. Emes and Kevin D. Sinclair
Int. J. Mol. Sci. 2021, 22(4), 1838; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041838 - 12 Feb 2021
Cited by 13 | Viewed by 3101
Abstract
One-carbon (1C) metabolism provides methyl groups for the synthesis and/or methylation of purines and pyrimidines, biogenic amines, proteins, and phospholipids. Our understanding of how 1C pathways operate, however, pertains mostly to the (rat) liver. Here we report that transcripts for all bar two [...] Read more.
One-carbon (1C) metabolism provides methyl groups for the synthesis and/or methylation of purines and pyrimidines, biogenic amines, proteins, and phospholipids. Our understanding of how 1C pathways operate, however, pertains mostly to the (rat) liver. Here we report that transcripts for all bar two genes (i.e., BHMT, MAT1A) encoding enzymes in the linked methionine-folate cycles are expressed in all cell types within the ovarian follicle, oocyte, and blastocyst in the cow, sheep, and pig; as well as in rat granulosa cells (GCs) and human KGN cells (a granulosa-like tumor cell line). Betaine-homocysteine methyltransferase (BHMT) protein was absent in bovine theca and GCs, as was activity of this enzyme in GCs. Mathematical modeling predicted that absence of this enzyme would lead to more volatile S-adenosylmethionine-mediated transmethylation in response to 1C substrate (e.g., methionine) or cofactor provision. We tested the sensitivity of bovine GCs to reduced methionine (from 50 to 10 µM) and observed a diminished flux of 1C units through the methionine cycle. We then used reduced-representation bisulfite sequencing to demonstrate that this reduction in methionine during bovine embryo culture leads to genome-wide alterations to DNA methylation in >1600 genes, including a cohort of imprinted genes linked to an abnormal fetal-overgrowth phenotype. Bovine ovarian and embryonic cells are acutely sensitive to methionine, but further experimentation is required to determine the significance of interspecific variation in BHMT expression. Full article
(This article belongs to the Special Issue Micronutrients in Metabolic Health)
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Review

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27 pages, 1920 KiB  
Review
Interaction between Metformin, Folate and Vitamin B12 and the Potential Impact on Fetal Growth and Long-Term Metabolic Health in Diabetic Pregnancies
by Manon D. Owen, Bernadette C. Baker, Eleanor M. Scott and Karen Forbes
Int. J. Mol. Sci. 2021, 22(11), 5759; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115759 - 28 May 2021
Cited by 26 | Viewed by 9511
Abstract
Metformin is the first-line treatment for many people with type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) to maintain glycaemic control. Recent evidence suggests metformin can cross the placenta during pregnancy, thereby exposing the fetus to high concentrations of metformin and [...] Read more.
Metformin is the first-line treatment for many people with type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) to maintain glycaemic control. Recent evidence suggests metformin can cross the placenta during pregnancy, thereby exposing the fetus to high concentrations of metformin and potentially restricting placental and fetal growth. Offspring exposed to metformin during gestation are at increased risk of being born small for gestational age (SGA) and show signs of ‘catch up’ growth and obesity during childhood which increases their risk of future cardiometabolic diseases. The mechanisms by which metformin impacts on the fetal growth and long-term health of the offspring remain to be established. Metformin is associated with maternal vitamin B12 deficiency and antifolate like activity. Vitamin B12 and folate balance is vital for one carbon metabolism, which is essential for DNA methylation and purine/pyrimidine synthesis of nucleic acids. Folate:vitamin B12 imbalance induced by metformin may lead to genomic instability and aberrant gene expression, thus promoting fetal programming. Mitochondrial aerobic respiration may also be affected, thereby inhibiting placental and fetal growth, and suppressing mammalian target of rapamycin (mTOR) activity for cellular nutrient transport. Vitamin supplementation, before or during metformin treatment in pregnancy, could be a promising strategy to improve maternal vitamin B12 and folate levels and reduce the incidence of SGA births and childhood obesity. Heterogeneous diagnostic and screening criteria for GDM and the transient nature of nutrient biomarkers have led to inconsistencies in clinical study designs to investigate the effects of metformin on folate:vitamin B12 balance and child development. As rates of diabetes in pregnancy continue to escalate, more women are likely to be prescribed metformin; thus, it is of paramount importance to improve our understanding of metformin’s transgenerational effects to develop prophylactic strategies for the prevention of adverse fetal outcomes. Full article
(This article belongs to the Special Issue Micronutrients in Metabolic Health)
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