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Ronaldo P Ferraris - One of the best experts on this subject based on the ideXlab platform.

  • cell type specific ketohexokinase dependent induction by fructose of lipogenic gene expression in mouse small intestine
    Journal of Nutrition, 2020
    Co-Authors: Arwa Aljawadi, Kunihiro Kishida, Chirag Patel, Reilly J. Shiarella, Emmanuellie Romelus, Madelyn J. Auvinen, Joshua Guardia, Sarah C. Pearce, Nan Gao, Ronaldo P Ferraris
    Abstract:

    BACKGROUND High intakes of fructose are associated with metabolic diseases, including hypertriglyceridemia and intestinal tumor growth. Although small intestinal epithelia consist of many different cell types, express lipogenic genes, and convert dietary fructose to fatty acids, there is no information on the identity of the cell type(s) mediating this conversion and on the effects of fructose on lipogenic gene expression. OBJECTIVES We hypothesized that fructose regulates the intestinal expression of genes involved in lipid and apolipoprotein synthesis, that regulation depends on the fructose Transporter solute carrier family 2 member a5 [Slc2a5 (Glucose Transporter 5)] and on ketohexokinase (Khk), and that regulation occurs only in enterocytes. METHODS We compared lipogenic gene expression among different organs from wild-type adult male C57BL mice consuming a standard vivarium nonpurified diet. We then gavaged twice daily for 2.5 d fructose or Glucose solutions (15%, 0.3 mL per mouse) into wild-type, Slc2a5-knockout (KO), and Khk-KO mice with free access to the nonpurified diet and determined expression of representative lipogenic genes. Finally, from mice fed the nonpurified diet, we made organoids highly enriched in enterocyte, goblet, Paneth, or stem cells and then incubated them overnight in 10 mM fructose or Glucose. RESULTS Most lipogenic genes were significantly expressed in the intestine relative to the kidney, liver, lung, and skeletal muscle. In vivo expression of Srebf1, Acaca, Fasn, Scd1, Dgat1, Gk, Apoa4, and Apob mRNA and of Scd1 protein increased (P < 0.05) by 3- to 20-fold in wild-type, but not in Slc2a5-KO and Khk-KO, mice gavaged with fructose. In vitro, Slc2a5- and Khk-dependent, fructose-induced increases, which ranged from 1.5- to 4-fold (P < 0.05), in mRNA concentrations of all these genes were observed only in organoids enriched in enterocytes. CONCLUSIONS Fructose specifically stimulates expression of mouse small intestinal genes for lipid and apolipoprotein synthesis. Secretory and stem cells seem incapable of transport- and metabolism-dependent lipogenesis, occurring only in absorptive enterocytes.

  • luminal fructose inhibits rat intestinal sodium phosphate coTransporter gene expression and phosphate uptake
    The American Journal of Clinical Nutrition, 2008
    Co-Authors: Séverine Kirchner, Anjali Muduli, Donatella M Casirola, Kannitha Prum, Veronique Douard, Ronaldo P Ferraris
    Abstract:

    Background: While searching by microarray for sugar-responsive genes, we inadvertently discovered that sodium-phosphate coTransporter 2B (NaPi-2b) mRNA concentrations were much lower in fructose-perfused than in Glucose-perfused intestines of neonatal rats. Changes in NaPi-2b mRNA abundance by sugars were accompanied by similar changes in NaPi-2b protein abundance and in rates of inorganic phosphate (Pi) uptake. Objective: We tested the hypothesis that luminal fructose regulates NaPi-2b. Design: We perfused into the intestine fructose, Glucose, and non-metabolizable or poorly transported Glucose analogs as well as phlorizin. Results: NaPi-2b mRNA concentrations and Pi uptake rates in fructose-perfused intestines were ≈30% of those in Glucose and its analogs. NaPi-2b inhibition by fructose is specific because the mRNA abundance and activity of the fructose Transporter GLUTS (Glucose Transporter 5) increased with fructose perfusion, whereas those of other Transporters were independent of the perfusate. Plasma Pi after 4 h of perfusion was independent of the perfusate, probably because normal kidneys can maintain normophosphatemia. Inhibiting Glucose-6-phosphatase, another fructose-responsive gene, with tungstate or vanadate nonspecifically inhibited NaPi-2b mRNA expression and Pi uptake in both Glucose- or fructose-perfused intestines. The AMP kinase (AMPK)-activator AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) enhanced and the fatty acid synthase-AMPK inhibitor C75 (3-carboxy-4-octyl-2-methylenebutyrolactone trans-4-carboxy-5-octyl-3-methylenebutyrolactone) prevented fructose inhibition of NaPi-2b but had no effect on expression of other Transporters. NaPi-2b expression decreased markedly with age and was inhibited by fructose in all age groups. Conclusions: Energy levels in enterocytes may play a role in NaPi-2b inhibition by luminal fructose. Consumption of fructose that supplies ≈10% of caloric intake by Americans clearly affects absorption of Pi and may promote Pi homeostasis in patients with impaired renal function.

Yoichi Nakazato - One of the best experts on this subject based on the ideXlab platform.

  • expression of Glucose Transporter 5 by microglia in human gliomas
    Neuropathology and Applied Neurobiology, 2004
    Co-Authors: Atsushi Sasaki, Haruyasu Yamaguchi, Y Horikoshi, G Tanaka, Yoichi Nakazato
    Abstract:

    Our previous studies indicate that Glucose Transporter 5 (GLUT5) is a microglial marker in routine paraffin sections, and is rarely present in monocytes/macrophages of the peripheral organs. We examined the expression of GLUT5 in 91 cases of human gliomas to characterize the microglial phenotype in glioma tissues. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections using such antibodies as a GLUT5 antibody, two markers for activated microglia: major histocompatibility complex (MHC) class II Ag and macrophage scavenger receptor class A (MSR-A), and MIB-1 antibody. The immunoreactivity of GLUT5 was present in three microglial phenotypes: ramified (resting), activated, and ameboid (macrophagic) microglia in most of the cases. A double-labelling study of astrocytic tumours using GLUT5 and MIB-1 antibodies demonstrated a proportion of proliferating microglia. However, no morphological difference between MIB-1-positive, microglial cells and MIB-1-negative, microglial cells was found. The number of GLUT5-positive microglia was significantly (P < 0.001) higher in astrocytic tumours than in oligodendroglial tumours. Many GLUT5-positive microglia (up to 52% in total cells) were often observed in pilocytic astrocytomas, where microglial cells were predominantly ramified, and the number of MHC class II- or MSR-A-positive microglia was less than GLUT5-positive microglia. Thus, the present study indicated that intrinsic microglia can be a source of microglia/macrophages cell populations in astrocytic tumours, and that pilocytic astrocytomas often have a high proportion of microglial cells with mild activation.

  • antiserum against human Glucose Transporter 5 is highly specific for microglia among cells of the mononuclear phagocyte system
    Neuroscience Letters, 2003
    Co-Authors: Atsushi Sasaki, Y Horikoshi, Yoichi Nakazato, Hideaki Yokoo, Haruyasu Yamaguchi
    Abstract:

    Human monocytes and a variety of tissue macrophages, including microglia, were studied immunohistochemically to determine the expression of a novel microglial marker, human Glucose Transporter 5 (hGLUT5), in these cells. The hGLUT5 was not expressed in most peripheral macrophages in the normal state, but weakly expressed in some foamy macrophages in atherosclerotic lesions. There was no hGLUT5 reactivity in blood monocytes. In the lesions of brain infarcts, foamy macrophages (predominantly monocyte-derived cells) in the ischemic core were mostly negative for hGLUT5, while activated and phagocytic microglia in the transitional zone were consistently positive. The present study indicated that unlike other microglial markers, hGLUT5 is rarely present in peripheral macrophages, and that hGLUT5 immunohistochemistry is useful in distinguishing microglia-derived macrophages from monocyte-derived macrophages in acute necrotic lesions.

Haruyasu Yamaguchi - One of the best experts on this subject based on the ideXlab platform.

  • expression of Glucose Transporter 5 by microglia in human gliomas
    Neuropathology and Applied Neurobiology, 2004
    Co-Authors: Atsushi Sasaki, Haruyasu Yamaguchi, Y Horikoshi, G Tanaka, Yoichi Nakazato
    Abstract:

    Our previous studies indicate that Glucose Transporter 5 (GLUT5) is a microglial marker in routine paraffin sections, and is rarely present in monocytes/macrophages of the peripheral organs. We examined the expression of GLUT5 in 91 cases of human gliomas to characterize the microglial phenotype in glioma tissues. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections using such antibodies as a GLUT5 antibody, two markers for activated microglia: major histocompatibility complex (MHC) class II Ag and macrophage scavenger receptor class A (MSR-A), and MIB-1 antibody. The immunoreactivity of GLUT5 was present in three microglial phenotypes: ramified (resting), activated, and ameboid (macrophagic) microglia in most of the cases. A double-labelling study of astrocytic tumours using GLUT5 and MIB-1 antibodies demonstrated a proportion of proliferating microglia. However, no morphological difference between MIB-1-positive, microglial cells and MIB-1-negative, microglial cells was found. The number of GLUT5-positive microglia was significantly (P < 0.001) higher in astrocytic tumours than in oligodendroglial tumours. Many GLUT5-positive microglia (up to 52% in total cells) were often observed in pilocytic astrocytomas, where microglial cells were predominantly ramified, and the number of MHC class II- or MSR-A-positive microglia was less than GLUT5-positive microglia. Thus, the present study indicated that intrinsic microglia can be a source of microglia/macrophages cell populations in astrocytic tumours, and that pilocytic astrocytomas often have a high proportion of microglial cells with mild activation.

  • antiserum against human Glucose Transporter 5 is highly specific for microglia among cells of the mononuclear phagocyte system
    Neuroscience Letters, 2003
    Co-Authors: Atsushi Sasaki, Y Horikoshi, Yoichi Nakazato, Hideaki Yokoo, Haruyasu Yamaguchi
    Abstract:

    Human monocytes and a variety of tissue macrophages, including microglia, were studied immunohistochemically to determine the expression of a novel microglial marker, human Glucose Transporter 5 (hGLUT5), in these cells. The hGLUT5 was not expressed in most peripheral macrophages in the normal state, but weakly expressed in some foamy macrophages in atherosclerotic lesions. There was no hGLUT5 reactivity in blood monocytes. In the lesions of brain infarcts, foamy macrophages (predominantly monocyte-derived cells) in the ischemic core were mostly negative for hGLUT5, while activated and phagocytic microglia in the transitional zone were consistently positive. The present study indicated that unlike other microglial markers, hGLUT5 is rarely present in peripheral macrophages, and that hGLUT5 immunohistochemistry is useful in distinguishing microglia-derived macrophages from monocyte-derived macrophages in acute necrotic lesions.

Atsushi Sasaki - One of the best experts on this subject based on the ideXlab platform.

  • expression of Glucose Transporter 5 by microglia in human gliomas
    Neuropathology and Applied Neurobiology, 2004
    Co-Authors: Atsushi Sasaki, Haruyasu Yamaguchi, Y Horikoshi, G Tanaka, Yoichi Nakazato
    Abstract:

    Our previous studies indicate that Glucose Transporter 5 (GLUT5) is a microglial marker in routine paraffin sections, and is rarely present in monocytes/macrophages of the peripheral organs. We examined the expression of GLUT5 in 91 cases of human gliomas to characterize the microglial phenotype in glioma tissues. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections using such antibodies as a GLUT5 antibody, two markers for activated microglia: major histocompatibility complex (MHC) class II Ag and macrophage scavenger receptor class A (MSR-A), and MIB-1 antibody. The immunoreactivity of GLUT5 was present in three microglial phenotypes: ramified (resting), activated, and ameboid (macrophagic) microglia in most of the cases. A double-labelling study of astrocytic tumours using GLUT5 and MIB-1 antibodies demonstrated a proportion of proliferating microglia. However, no morphological difference between MIB-1-positive, microglial cells and MIB-1-negative, microglial cells was found. The number of GLUT5-positive microglia was significantly (P < 0.001) higher in astrocytic tumours than in oligodendroglial tumours. Many GLUT5-positive microglia (up to 52% in total cells) were often observed in pilocytic astrocytomas, where microglial cells were predominantly ramified, and the number of MHC class II- or MSR-A-positive microglia was less than GLUT5-positive microglia. Thus, the present study indicated that intrinsic microglia can be a source of microglia/macrophages cell populations in astrocytic tumours, and that pilocytic astrocytomas often have a high proportion of microglial cells with mild activation.

  • antiserum against human Glucose Transporter 5 is highly specific for microglia among cells of the mononuclear phagocyte system
    Neuroscience Letters, 2003
    Co-Authors: Atsushi Sasaki, Y Horikoshi, Yoichi Nakazato, Hideaki Yokoo, Haruyasu Yamaguchi
    Abstract:

    Human monocytes and a variety of tissue macrophages, including microglia, were studied immunohistochemically to determine the expression of a novel microglial marker, human Glucose Transporter 5 (hGLUT5), in these cells. The hGLUT5 was not expressed in most peripheral macrophages in the normal state, but weakly expressed in some foamy macrophages in atherosclerotic lesions. There was no hGLUT5 reactivity in blood monocytes. In the lesions of brain infarcts, foamy macrophages (predominantly monocyte-derived cells) in the ischemic core were mostly negative for hGLUT5, while activated and phagocytic microglia in the transitional zone were consistently positive. The present study indicated that unlike other microglial markers, hGLUT5 is rarely present in peripheral macrophages, and that hGLUT5 immunohistochemistry is useful in distinguishing microglia-derived macrophages from monocyte-derived macrophages in acute necrotic lesions.

Kwokpui Fung - One of the best experts on this subject based on the ideXlab platform.

  • inhibition of cell proliferation in human breast tumor cells by antisense oligonucleotides against facilitative Glucose Transporter 5
    Journal of Cellular Biochemistry, 2004
    Co-Authors: Kwokkeung Chan, Judy Yuetwa Chan, Karen K W Chung, Kwokpui Fung
    Abstract:

    In recent years, successful examples of antisense oligonucleotide (AS) therapy for genetic diseases have stimulated scientists to investigate its application on cancer diseases. AS can be used to down-regulate the mRNA and protein expression by annealing to specific region of the target mRNA which is responsible for the malignancy. Glucose Transporter 5 (Glut5) is a tissue specific Transporter that can be found on breast cancer tissues but not on normal breast tissues. Therefore, it is of clinical interest to investigate whether AS against Glut5 mRNA can tackle breast cancer. In this study, two cell lines, MCF-7 which is estrogen-receptor positive and MDA-MB-231 which is estrogen-receptor negative, were used to mimic breast cancer tissues at early and late stages, respectively. A 15-base sequence around the start codon of Glut5 was used. It was found that AS against Glut5 exerted anti-proliferative effect on both of these two breast tumor cell lines and seemed to exert its effect via the suppression of expression of Glut5 proteins in the cells. AS against Glut5 exhibited no effect on human hepatoma HepG2 cells which do not possess any Glut5. The results imply an alternative way in treating breast tumor as the AS against Glut5, unlike tamoxifen, takes effect on breast tumor cells via suppressing the expression of Glut5 that they specifically possess, and regardless whether the breast tumors are estrogen dependent or not.