Tohru Matsui

Kyoto University, Kioto, Kyōto, Japan

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Publications (81)106.42 Total impact

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    ABSTRACT: The BMP pathway positively regulates murine brown adipogenesis. We herein examined the mRNA levels of BMPs and activin βB as well as receptors for the BMP pathway in the adipose tissues of cattle fed diets with a differential ratio of concentrate to roughage or a vitamin A-deficient diet. The expression of activin βB was significantly increased in the subcutaneous fat depot of animals fed the concentrate diet, while the vitamin A-deficient diet significantly increased the expression of BMP4 in the mesenteric fat depot. The expression of receptors for the BMP pathway, ALK2, ALK3, ActRIIA, and BMPR2, showed a similar pattern to that of BMP4 and activin βB in response to the dietary treatments. The results of the present study demonstrated that diet modulated the expression of components of the BMP pathway and may be responsible for the regulatory expression of brown/beige adipocyte-related genes in the adipose tissues of cattle.
    Livestock Science 02/2015; DOI:10.1016/j.livsci.2015.02.008 · 1.10 Impact Factor
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    ABSTRACT: Expression of hepcidin, a central regulator of systemic iron metabolism, is transcriptionally regulated by the bone morphogenetic protein (BMP) pathway. However, the factors other than the BMP pathway also participate in the regulation of hepcidin expression. In the present study, we show that serum treatment increased hepcidin expression and transcription without inducing the phosphorylation of Smad1/5/8 in primary hepatocytes, HepG2 cells or Hepa1-6 cells. Co-treatment with LDN-193189, an inhibitor of the BMP type I receptor, abrogated this hepcidin induction. Reporter assays using mutated reporters revealed the involvement of the BMP response element-1 (BMP-RE1) and signal transducers and activator of transcription (STAT)- and activator protein (AP)-1-binding sites in serum-induced hepcidin transcription in HepG2 cells. Serum treatment induced the expression of the AP-1 components c-fos and junB in primary hepatocytes and HepG2 cells. Forced expression of c-fos or junB enhanced the response of hepcidin transcription to serum treatment. By contrast, expression of dominant negative (dn)-c-fos and dn-junB decreased hepcidin transcription. The present study reveals that serum contains factors stimulating hepcidin transcription. Basal BMP activity is essential for the serum-induced hepcidin transcription, although serum treatment does not stimulate the BMP pathway. The induction of c-fos and junB by serum treatment stimulates hepcidin transcription, through possibly cooperation with BMP-mediated signaling. Considering that AP-1 is induced by various stimuli, the present results suggest that hepcidin expression is regulated by more diverse factors than had been previously considered.
    Gene 08/2014; 551(2). DOI:10.1016/j.gene.2014.08.037 · 2.20 Impact Factor
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    ABSTRACT: Hepcidin produced in the liver negatively regulates intestinal iron absorption, and the bone morphogenetic protein (BMP) pathway is well-known to stimulate hepcidin expression. However, the regulation of hepcidin expression has not been fully elucidated. In this study, we evaluate different systems that can be used to determine how hepcidin expression is regulated. The basal expression of hepcidin in liver cell lines, such as HepG2 cells and Hepa1-6 cells, was lower than that in the liver and primary hepatocytes; the expression levels of hepcidin in the cell lines were near the limit of detection for RT-PCR and RT-qPCR analyses. Treatment with trichostatin A, RNAlater, or MG-132 enhanced the expression of hepcidin in HepG2 cells, suggesting that histone deacetylation, instability of mRNA, or proteosomal degradation of the protein(s) that positively regulate hepcidin expression may be responsible for the decreased expression of hepcidin in HepG2 cells. In luciferase-based reporter assays, BMP induced the transcription of a reporter, hepcidin(− 2018)-luc, that contains nt − 2018 through nt − 35 of the hepcidin promoter in HepG2 cells and Hepa1-6 cells. However, BRE-luc, a representative reporter used to evaluate BMP signaling, was unresponsive to BMP in HepG2 cells. These results suggest that hepcidin transcription can be best evaluated in liver cell lines and that the hepcidin promoter senses BMP signaling with high sensitivity. The present study demonstrates that studies regarding the regulation of hepcidin expression at the mRNA level should be evaluated in primary hepatocytes, and liver cell lines are well-suited for studies examining the transcriptional regulation of hepcidin.
    Gene 08/2014; 546(1):50–55. DOI:10.1016/j.gene.2014.05.040 · 2.20 Impact Factor
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    ABSTRACT: We previously reported the presence of brown/beige adipocytes in the white fat depots of mature cattle. The present study examined the effects of dietary vitamin A on the expression of brown/beige adipocyte-related genes in the white fat depots of fattening cattle. No significant differences were observed in the expression of Ucp1 between vitamin A-deficient cattle and control cattle. However, the expression of the other brown/beige adipocyte-related genes was slightly higher in the mesenteric fat depots of vitamin A-deficient cattle. The present results suggest that a vitamin A deficiency does not markedly affect the expression of Ucp1 in white fat depots, but imply that it may stimulate the emergence of beige adipocytes in the mesenteric fat depots of fattening cattle.
    Journal of Veterinary Medical Science 05/2014; DOI:10.1292/jvms.14-0137 · 0.88 Impact Factor
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    ABSTRACT: Previous studies indicate that muscle Pgc-1α expression governs the proportion of muscle fibre types. As a first step in using diet to manipulate the proportion of muscle fibre types by using Pgc-1α expression, the present study investigates the modulation of Pgc-1α expression by feedstuffs. A luciferase-based Pgc-1α reporter construct (Pgc-1α(-2553)-luc) that contains the mouse Pgc-1α promoter (-2553 to +78 bp) was prepared. A screen of ethanol extracts from 33 feedstuffs indicated that oolong tea and roasted green tea extracts decreased Pgc-1α(-2553)-luc expression in C2C12 myoblasts. The transcriptional repression of Pgc-1α by tea leaf extracts was reproduced in hepatic HepG2 cells. We further examined the effects of the alcohol extracts of tea waste and its silage on Pgc-1α transcription; the tea waste silage extract inhibited Pgc-1α transcription. Treatment with the extracts of raw tea leaves, tea waste and tea waste silage effectively decreased Pgc-1α mRNA levels during myogenesis of myosatellite cells. The present results suggest that tea leaves and their by-products could be used to modulate proportions of muscle fibre types. Copyright © 2013 John Wiley & Sons, Ltd.
    Cell Biochemistry and Function 04/2014; 32(3). DOI:10.1002/cbf.3006 · 2.13 Impact Factor
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    ABSTRACT: There are two types of brown adipocytes: classical brown adipocytes that form the brown fat depots and beige adipocytes that emerge in the white fat depots. Beige adipocytes have a low level of uncoupling protein 1 (Ucp1) expression in the basal state, but Ucp1 expression is increased in response to β adrenergic receptor activation. The present study explored the factors responsible for the differentiation of 3T3-L1 white preadipocytes to beige adipocytes. Significant expression of Ucp1 was not detected under any tested conditions in the absence of isoproterenol (Iso), an agonist of β adrenergic receptor. Iso-induced Ucp1 expression was significantly higher in the cells treated with a mixture of triiodothyronine (T3) and 3-isobutyl-1-methylxanthine (IBMX) for days 0-8 than in the control cells. Chronic IBMX treatment was indispensable for the enhanced Iso-induced Ucp1 expression, and treatment with additional rosiglitazone (Rosi) for days 0-8 further increased the Ucp1 expression. Recently, genes were identified that are predominantly expressed in beige adipocytes, which were induced from stromal vascular cells in white fat depots. However, the expression levels of the beige adipocyte-selective genes in the adipocytes induced by the mixture of T3, IBMX and Rosi did not differ from those in the control adipocytes. The present study indicates that 3T3-L1 cells can differentiate to beige-like adipocytes by prolonged treatment with the mixture of T3, IBMX and Rosi, and that the gene expression profile of the adipocytes is distinct from those previously induced from white fat depots.
    Journal of Veterinary Medical Science 09/2013; 76(1). DOI:10.1292/jvms.13-0359 · 0.88 Impact Factor
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    ABSTRACT: We previously revealed that endogenous bone morphogenetic protein (Bmp) activity is required for lipid accumulation in 3T3-L1 adipocytes. The present study characterized the role of endogenous Bmp activity in preadipocytes. Endogenous Bmp activity was monitored by analyzing the level of phosphorylation of Smad1/5/8, downstream molecules in the Bmp pathway. Higher levels of phosphorylated Smad1/5/8 were detected in adipogenic cells but not in non-adipogenic cells prior to differentiation induction. The inhibition of the Bmp pathway during this period decreased the expression of Pparγ2 and C/ebpα, which are transcription factors responsible for adipocyte differentiation. The expression of these transcription factors were also down-regulated by Bmp4 knockdown. In addition, endogenous Bmp4 was required for the repression of Intrleukin-11 expression. Endogenous Bmp4 in preadipocytes is indispensable for the onset of the adipogenic program, and may help to maintain the preadipocytic state during adipocyte differentiation.
    Cytokine 08/2013; DOI:10.1016/j.cyto.2013.07.011 · 2.87 Impact Factor
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    ABSTRACT: Brown adipocytes generate heat through the expression of mitochondrial Ucp1. Compared with the information on the regulatory differentiation of white preadipocytes, the factors affecting brown adipogenesis are not as well understood. The present study examined the roles of the Tgf-β family members Bmp, Tgf-β and Activin during differentiation of HB2 brown preadipocytes. Endogenous Bmp activity and effects of exogenous Tgf-β family members were examined. Role of Srebp1c in brown adipogenesis was further explored. Although Bmp7 has been suggested to be a potent stimulator of brown adipogenesis, it affected neither the expression of brown adipocyte-selective genes nor Ucp1 induction in response to a β adrenergic receptor agonist. Unlike in 3T3-L1 white preadipocytes, endogenous Bmp activity was not required for brown adipogenesis; treatment with inhibitors of the Bmp pathway did not affect differentiation of preadipocytes. Administration of Tgf-β1 or Activin A efficiently decreased the insulin-induced expression of brown adipocyte-selective genes. Tgf-β1 and Activin A decreased the expression of Pparγ2 and C/ebpα, suggesting the inhibition of adipogenesis. The Tgf-β- and Activin-induced inhibition of brown adipogenesis was mediated by the repression of Srebp1c expression; Tgf-β1 and Activin A blocked Srebp1c gene induction in response to the differentiation induction, and knock-down of Srebp1 expression inhibited brown adipogenesis. Endogenous Bmp is dispensable for brown adipogenesis, and Srebp1c is indispensable, which is negatively regulated by Tgf-β and Activin. Control of activity of the Tgf-β family is potentially useful for maintenance of energy homeostasis through manipulation of brown adipogenesis.
    Biochimica et Biophysica Acta 07/2013; DOI:10.1016/j.bbagen.2013.06.036 · 4.66 Impact Factor
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    ABSTRACT: Brown adipocytes, which regulate non-shivering thermogenesis, have been believed to exist in a limited number of mammalian species, and only under limited physiological conditions. Recent discoveries indicate that adult humans possess a significant number of functional brown adipocytes. This study explores the regulatory emergence of brown adipocytes in white adipose tissue (WAT) depots of fattening cattle. RT-PCR analyses indicated significant expression of Ucp1, a brown adipocyte-specific gene, in the WAT of 31-month-old Japanese Black steers. Immunohistochemical analysis revealed that Ucp1-positive small adipocytes were dispersed in the subcutaneous WAT. Next, we examined expression level of Ucp1 and other brown adipocyte-selective genes such as Pgc1α, Cidea, Dio2, Cox1, Cox7a1 and Cox8b in WAT of 30-month-old steers fed either diet with low protein/energy content (roughage diet) or that with high protein/energy content (concentrate diet) for 20 months. Ucp1 expression in the subcutaneous WAT was significantly higher in the concentrate diet group than in the roughage diet group. Furthermore, the higher Ucp1 expression levels were limited to the subcutaneous WAT, and no differences between groups were detected in the mesenteric, perirenal, intermuscular or intramuscular WAT. Expression of Dio2, Cox1 and Cox8b was higher in the subcutaneous WAT but not in the mesenteric WAT of the concentrate diet group. Furthermore, expression of Prdm16, a positive regulator of differentiation toward brown adipocyte-lineage cells, and expression of leptin, a molecule that enhances activity of brown adipocytes, were significantly higher in the subcutaneous WAT of the concentrate diet group. This study demonstrates the presence of brown adipocytes in WAT depots of fattening cattle, and suggests the diet-related modulation of expression of genes predominantly expressed in brown adipocytes.
    General and Comparative Endocrinology 01/2013; DOI:10.1016/j.ygcen.2013.01.006 · 2.82 Impact Factor
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    ABSTRACT: Mast cells, multifunctional effector cells of the immune system, are implicated in the pathogenesis of hepatic steatosis and fibrosis. Magnesium (Mg) deficiency was reported to increase triglyceride concentration in the liver, and to exacerbate the collagen deposition induced by carbon tetrachloride in the liver. Although Mg deficiency increases mast cells in the small intestine, the kidney and bone marrow, the effect of Mg deficiency on mast cells has not been clarified in the liver. We examined the emergence of mast cells in the liver of Sprague-Dawley rats given an Mg-deficient diet. Rats were fed a control diet or an Mg-deficient diet for 4 wk. Mg deficiency increased the levels of mRNA known to be expressed by mast cells in the liver; the mRNA of α- and β-chain high-affinity immunoglobulin E receptor (FcεR1α, FcεR1β), and the mRNA of mast cell protease 1 (Mcpt1), and mast cell protease 2 (Mcpt2). Histological observation showed that some mast cells were locally distributed around portal triads in the Mg-deficient group but mast cells were scarcely found in the control group. These results clearly indicate that Mg deficiency induces the emergence of mast cells around portal triads of the liver in Sprague-Dawley rats.
    Journal of Nutritional Science and Vitaminology 01/2013; 59(6):560-3. DOI:10.3177/jnsv.59.560 · 0.99 Impact Factor
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    ABSTRACT: Our previous report indicated that magnesium (Mg) deficiency increased molybdenum (Mo) concentration in the rat liver, suggesting the possibility that Mg deficiency affects Mo metabolism. Growing male rats were given a control diet or a Mg-deficient diet for 4 weeks. Urine and feces were collected during the second and fourth weeks of the feeding trial. The liver, kidney, spleen, skeletal muscle, and blood were collected at the end of the feeding trial. Mg deficiency did not affect the apparent absorption of Mo, but it reduced urinary excretion of Mo. The retention of Mo tended to be higher in the Mg-deficient group than in the control group. Hepatic Mo concentration was higher in the Mg-deficient group than in the control group, but Mg deficiency did not affect Mo concentration in other tissues and plasma. Mg deficiency downregulated the mRNA expression of Mo transporter 2 (MOT2) in the liver, but not in the kidney. These results suggest that Mg deficiency decreases urinary Mo excretion, which is too slight to affect plasma Mo concentration, and that Mg deficiency selectively disturbs the homeostatic mechanism of Mo in the liver, which is not related to the mRNA expression of MOT2 in the liver.
    Biological trace element research 11/2012; DOI:10.1007/s12011-012-9541-3 · 1.92 Impact Factor
  • Eri Nakamura, Hiroki Yokota, Tohru Matsui
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    ABSTRACT: Many edible seaweeds are rich in magnesium (Mg). However, Mg absorption is low in some seaweeds because fibers in these seaweeds suppress Mg absorption. We hypothesize that Mg absorption from some other seaweeds is not low because of the diversity of fibers. We measured Mg concentration and Mg solubility after in vitro digestion in edible seaweeds, Aosa (Ulvaceae pertusa), Kombu (Laminaria japonica) and Funori (Gloiopeltis furcata). Then we determined Mg absorption in rats given diets containing these seaweeds or magnesium oxide as the major source of Mg, and calculated Mg absorption from seaweeds. The fractional apparent absorption of Mg in seaweeds was Kombu = magnesium oxide > Aosa = Funori. Mg concentration was Aosa > Kombu and Funori had an intermediate amount of Mg, while Mg solubility after in vitro digestion was Funori = Kombu > Aosa. Consequently, the absorbable Mg concentration was Aosa = Kombu > Funori. The absorption of Mg from different seaweeds differs and is not affected by the Mg solubility alone. The absorbable Mg concentration was high in Aosa and in Kombu, indicating that Aosa and Kombu are good sources of Mg.
    Journal of the Science of Food and Agriculture 08/2012; 92(11):2305-9. DOI:10.1002/jsfa.5626 · 1.88 Impact Factor
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    ABSTRACT: To date, minerals of interest have been analyzed individually to understand mineral dynamics and metabolism. Our recent development of metallomic analyses enabled us to evaluate minerals in an unbiased and global manner. Here, we evaluated the effects of ingestion of excess zinc to plasma and tissue concentrations of minerals in growing rats. A total of 26 minerals were simultaneously evaluated by metallomic analyses using inductively coupled plasma-mass spectrometry (ICP-MS) in semi-quantification mode; the concentrations of several minerals exhibited consistent changes in response to the concentrations of dietary zinc. Manganese concentrations in plasma and femur increased, while concentrations in the liver and pancreas decreased with increasing dietary zinc concentrations. Because the interaction between zinc and manganese is not known, we further focused our analysis on liver manganese. Quantitative analyses also indicated that the hepatic concentration of manganese decreased in response to the ingestion of diets containing excess zinc, a result that is partly explained by the decreased expression of hepatic Zip8, a manganese transporter. The present study reveals mineral interaction by using metallomic analyses and proposes a possible mechanism that underlies this novel interaction.
    Metallomics 06/2012; 4(8):847-50. DOI:10.1039/c2mt20100c · 4.10 Impact Factor
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    ABSTRACT: Mg deficiency increases the concentration of Zn in the liver. We investigated the effect of Mg deficiency on the expression of Zn-regulating factors such as Zn transporters and metallothionein (MT) in the rat liver. Because Ca deficiency alleviates some of the effects of Mg deficiency, we also investigated the interactions associated with Ca and Mg deficiencies. Growing male rats were given a control diet, a Mg-deficient diet, a Ca-deficient diet and a Mg- and Ca-deficient diet for 3 weeks. Mg and Ca deficiencies additively increased the mRNA levels of MT-1 and MT-2, the MT protein concentration and the concentration of Zn in the liver. The hepatic mRNA level of Zip14 increased with Mg deficiency but not with Ca deficiency. The dietary treatments did not affect the mRNA levels of other Zn transporters such as Zip1, Zip5, ZnT1, ZnT5 and ZnT6 in the liver. Ca deficiency was found to decrease the amount of femoral Zn and increase serum Zn concentration. This did not occur in the case of Mg deficiency. These results suggest that Mg deficiency enhances hepatic Zn uptake by the up-regulation of Zip14 expression and increases hepatic Zn concentration, leading to the enhancement of MT expression. Ca deficiency causes a transfer of Zn from the bone to the liver, which increases hepatic Zn concentration and, in turn, up-regulates the expression of MT. Because Mg and Ca deficiencies increase hepatic Zn concentration and increase MT expression by different mechanisms, their effects are additive.
    The British journal of nutrition 05/2012; 109(3):1-8. DOI:10.1017/S0007114512001195 · 3.45 Impact Factor
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    ABSTRACT: It is hypothesized that magnesium (Mg) absorption from mineral water is affected by the concentration of Mg in the water, the consumption pattern, and the volume consumed per serving. The present study examined the effect of serving volume and consumption pattern of artificial mineral water (AMW) and Mg concentration on Mg absorption in rats. Magnesium in AMW was labeled with magnesium-25 as a tracer. Each group consisted of 6 or 7 rats. In experiment 1, the rats received 1 mL of AMW containing 200 mg Mg/L at 4 times, 400 mg Mg/L twice, or 800 mg Mg/L at 1 time. In experiment 2, the rats received 1 mL of AMW containing 200 mg Mg/L or 0.25 mL of AMW containing 800 mg Mg/L at 4 times or 1 mL of AMW containing 800 mg Mg/L at 1 time. The absorption of Mg decreased with increasing Mg concentrations in the same serving volume of AMW with different serving frequencies. When the AMW containing 800 mg Mg/L was portioned into 4 servings, Mg absorption increased to the level of absorption in the group exposed to AMW containing 200 mg Mg/L served at the same frequency. These results suggest that the Mg concentration and the volume of AMW do not affect Mg absorption per se, but Mg absorption from AMW decreases when the amount of Mg in each serving is increased. Thus, frequent consumption is preferable for mineral water rich in Mg when the total consumption of mineral water is the same.
    Nutrition research 01/2012; 32(1):59-65. DOI:10.1016/j.nutres.2011.11.001 · 2.59 Impact Factor
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    ABSTRACT: Magnesium (Mg) deficiency induces the production of free radicals, increases cytosolic ionized calcium concentration, and modulates the function of skeletal muscle in rats. The present study examined the effects of Mg deficiency on the gene expression of molecules related to myogenesis in the gastrocnemius muscle as well as in C2C12 myogenic cells. Ingestion of an Mg-deficient diet resulted in a lower weight of the gastrocnemius muscle and higher concentration of muscular TBARSs, an index of oxidative stress. Mg deficiency also enhanced the expression of Myod and myogenin. In vivo effects of Mg deficiency on myogenic gene expression were partially reproduced in in vitro C2C12 cells; expression of Myod was up-regulated by a mixed culture of myoblasts and myotubes with Mg-deficient medium, which related to the simultaneous up-regulation of Myhc IIb, a myotube-specific protein. The culture with Mg-deficient medium did not increase the gene transcript level of HO-1, another marker of oxidative stress, suggesting that Mg deficiency-induced Myod expression does not result from oxidative stress. Furthermore, oxidative stress induced by hydrogen peroxide did not increase Myod expression, whereas the expression of Myod, myogenin and Myhc IIb was decreased by oxidative stress from the initial phase of differentiation. The effects of Mg deficiency depended on the stages of myogenesis; myoblast culture in Mg-deficient differentiation medium did not affect the expression of Myod and Myhc IIb. The present study revealed stage-dependent effects of Mg deficiency on myogenesis.
    Cell Biochemistry and Function 10/2011; 29(7):577-81. DOI:10.1002/cbf.1790 · 2.13 Impact Factor
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    ABSTRACT: Our previous study revealed the indispensable activity of endogenous bone morphogenetic protein (Bmp) prior to differentiation induction of C2C12 myoblasts for myogenesis. Here we investigated the Bmp isoform responsible for endogenous Bmp activity during differentiation and its role in myogenesis. Gene expression of Bmp4 during myogenesis was evaluated in C2C12 cells. Effects of inhibition of the Bmp pathway on myogenesis were examined. Cells expressing Bmp4 and regulation of Bmp4 expression in myoblasts were explored. The expression of Bmp4 increased with the progression of myogenesis, although the extent of the increase after differentiation induction was smaller than that before the induction. Down-regulation of Bmp signal components including Bmp4, Bmpr2, and Alk2/3 inhibited the emergence of positive cells for myosin heavy chain II. The treatments also decreased the Myogenin expression. Treatment with cytosine arabinoside decreased the expression of Bmp4. Also, Bmp4 expression was also lower in isolated myotubes than in residual cells. Expression of Rgm c was higher in the myotube fraction. Transcription of Bmp4 was repressed by the conditioned medium of mixed cells consisting of myoblasts and myotubes. Bmp4 expressed in myoblasts has a positive role in myotube formation/maturation through myogenin expression. The presence of myotubes inhibits Bmp4 expression in proliferating myoblasts through transcriptional regulation, although the expression is intrinsically increased with time of culture. Taken previous results on involvement of Bmp in the commitment of osteoblasts and adipocytes with the present results together, Bmp may act as a general promoter of mesenchymal cell differentiation.
    Biochimica et Biophysica Acta 09/2011; 1810(12):1127-35. DOI:10.1016/j.bbagen.2011.09.008 · 4.66 Impact Factor
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    ABSTRACT: The growth of weaning piglets is effectively improved by feeding a high-Zn diet (3000 mg Zn/kg of diet). The present study examined whether feeding a diet supplemented with Zn (1016-3000 mg/kg) for 10 d induces growth benefits in rats. In addition, tissue weight, Zn content of tissues and expression of Zn transporters were examined in these rats. Zn supplementation did not significantly increase body weight. Breaking line model analyses indicated that the weight of the pancreas, the organ most sensitive to excess Zn, significantly decreased with increasing Zn intake beyond 15·2 mg/d. Excess Zn has been suggested to accumulate in the liver, kidney and bone in order to protect the pancreas. Zn concentrations in the plasma, liver, kidney and femur increased with increasing Zn intake up to approximately 30 mg/d, whereas those in the pancreas increased up to 8·4 mg/d and decreased by Zn intake beyond 8·4 mg/d. The expression levels of the Zn transporters Zip4 and ZnT1 in the intestinal epithelium were significantly lower in rats fed a diet supplemented with 1016 mg/kg Zn compared to those fed the basal diet. The present study reveals that (1) excess Zn intake does not accelerate growth in rats, but is detrimental to the pancreas, (2) the excess Zn is effectively accumulated in the liver, kidney and bone, without sufficient protection of the pancreas and (3) expression of Zn transporters is down-regulated in response to excess Zn intake.
    The British journal of nutrition 09/2011; 107(11):1655-63. DOI:10.1017/S0007114511004867 · 3.45 Impact Factor
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    ABSTRACT: Mg deficiency accelerates Fe accumulation in the liver, which may induce various metabolic disturbances. In the present study, we examined the gene expression of Hepcidin, a peptide hormone produced in the liver to regulate intestinal Fe absorption negatively, in Mg-deficient rats. Although liver Fe concentration was significantly higher in rats fed an Mg-deficient diet for 4 weeks than in rats fed a control diet, Hepcidin expression in the liver was comparable between the dietary groups. Previous studies revealed that Fe overload up-regulated Hepcidin expression through transcriptional activation by Fe-induced bone morphogenetic protein (Bmp) 6, a growth/differentiation factor belonging to the transforming growth factor-β family, in the liver. Mg deficiency up-regulated the expression of Bmp6 but did not affect the expression of inhibition of DNA binding 1, a sensitive Bmp-responsive gene. In addition, the expression of Bmp receptors such as activin receptor-like kinase 2 (Alk2), activin receptor type IIA (Actr2a), activin receptor type IIB (Actr2b) and Bmp type II receptor (Bmpr2) was lower in the liver of Mg-deficient rats than in that of control rats. The present study indicates that accumulation of hepatic Fe by Mg deficiency is a stimulant inducing Bmp6 expression but not Hepcidin expression by blunting Bmp signalling possibly resulting from down-regulation of the receptor expression. Unresponsive Hepcidin expression may have a role in Mg deficiency-induced changes related to increased liver Fe.
    The British journal of nutrition 05/2011; 106(8):1169-72. DOI:10.1017/S0007114511001553 · 3.45 Impact Factor
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    ABSTRACT: Magnesium (Mg) deficiency is well known to affect metabolism of some trace minerals. We investigated the effect of Mg deficiency on hepatic concentration of various minerals in rats. Twelve 5-week-old male rats were divided into the groups given a control diet and an Mg-deficient diet. After 4 weeks, liver sample was collected from each rat. The concentrations of 36 minerals were simultaneously determined by a semiquantitative method of inductively coupled plasma-mass spectrometry (ICP-MS). The semiquantitative analysis showed that Mg deficiency significantly increased iron (Fe), copper (Cu), zinc (Zn), gallium (Ga), yttrium (Y), zirconium (Zr), molybdenum (Mo), rhodium (Rh), silver (Ag), and barium (Ba) concentrations, and significantly decreased scandium (Sc) and niobium (Nb) concentrations in rat liver. Then, hepatic Fe, Cu, Zn, Sc, Zr, and Mo concentrations were quantitatively measured, which indicated the similar effects as observed by the semiquantitative analysis. Additionally, the semiquantitative measurements of these minerals were highly correlated to these measurements with the quantitative method, but the measurements were not completely consistent between these analyses. The present study is the first research indicating the changes of hepatic Ga, Y, Zr, Mo, Rh, Ag, Ba, Sc, and Nb concentrations in Mg-deficient rats. The present study also indicates that the semiquantitative analysis with ICP-MS is a valid method for screening analysis to investigate various mineral concentrations in animal tissues.
    Biological trace element research 04/2011; 144(1-3):865-71. DOI:10.1007/s12011-011-9042-9 · 1.92 Impact Factor