Skip to main content
Erschienen in: Inflammation 1/2018

30.09.2017 | ORIGINAL ARTICLE

FGF-21 Plays a Crucial Role in the Glucose Uptake of Activated Monocytes

verfasst von: Nan Wang, Jun-Yan Li, Ting-ting Zhao, Si-ming Li, Cheng-Bin Shen, De-Shan Li, Wen-Fei Wang

Erschienen in: Inflammation | Ausgabe 1/2018

Einloggen, um Zugang zu erhalten

Abstract

Monocytes display a gradual change in metabolism during inflammation. When activated, the increase in glucose utilization is important for monocytes to participate in immune and inflammatory responses. Further studies on the mechanism underlying this biological phenomenon may provide a new understanding of the relationship between immune response and metabolism. The THP-1 cells were used as a monocyte model. The cells were activated with lipopolysaccharide (LPS). Glucose uptake was measured using flow cytometry. The expression of fibroblast growth factor 21 (FGF-21), glucose transporter 1 (GLUT-1), and other FGF-21 signaling pathway-related factor mRNAs was determined by real-time polymerase chain reaction. Further, the relationship between FGF-21 expression in monocytes and phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) signaling pathway was determined by Western blotting. LPS elevated FGF-21 expression in monocytic THP-1 cells in vitro. Functional assays showed that the phenomenon in which LPS and FGF-21 stimulated glucose uptake in monocytic THP-1 cells could be inhibited by FGFR inhibitor. The mechanism of elevation of FGF-21 was found to involve the PI3K/Akt signaling pathway. This study indicated that FGF-21 could regulate the immune response indirectly by influencing the glucose uptake of activated monocytes cells.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Palmer, C.S., J.J. Anzinger, Z. Jingling, et al. 2014. Glucose transporter 1-expressing proinflammatory monocytes are elevated in combination antiretroviral therapy-treated and untreated HIV+ subjects. The Journal of Immunology 193 (11): 5595–5603.CrossRefPubMed Palmer, C.S., J.J. Anzinger, Z. Jingling, et al. 2014. Glucose transporter 1-expressing proinflammatory monocytes are elevated in combination antiretroviral therapy-treated and untreated HIV+ subjects. The Journal of Immunology 193 (11): 5595–5603.CrossRefPubMed
2.
Zurück zum Zitat Calder, P., G. Dimitriadis, and P. Newsholme. 2007. Glucose metabolism in lymphoid and inflammatory cells and tissues. Current Opinion in Clinical Nutrition & Metabolic Care 10 (4): 531–540.CrossRef Calder, P., G. Dimitriadis, and P. Newsholme. 2007. Glucose metabolism in lymphoid and inflammatory cells and tissues. Current Opinion in Clinical Nutrition & Metabolic Care 10 (4): 531–540.CrossRef
3.
Zurück zum Zitat Calder, P.C. 1995. Fuel utilization by cells of the immune system. Proceedings of the Nutrition Society 54 (1): 65–82.CrossRefPubMed Calder, P.C. 1995. Fuel utilization by cells of the immune system. Proceedings of the Nutrition Society 54 (1): 65–82.CrossRefPubMed
4.
Zurück zum Zitat Maratou, E., G. Dimitriadis, A. Kollias, et al. 2007. Glucose transporter expression on the plasma membrane of resting and activated white blood cells. European Journal of Clinical Investigation 37 (4): 282–290.CrossRefPubMed Maratou, E., G. Dimitriadis, A. Kollias, et al. 2007. Glucose transporter expression on the plasma membrane of resting and activated white blood cells. European Journal of Clinical Investigation 37 (4): 282–290.CrossRefPubMed
5.
Zurück zum Zitat Palsson-Mcdermott, E.M., and L.A.J. O'Neill. 2013. The Warburg effect then and now: from cancer to inflammatory diseases. Bioessays News & Reviews in Molecular Cellular & Developmental Biology 35 (11): 965–973.CrossRef Palsson-Mcdermott, E.M., and L.A.J. O'Neill. 2013. The Warburg effect then and now: from cancer to inflammatory diseases. Bioessays News & Reviews in Molecular Cellular & Developmental Biology 35 (11): 965–973.CrossRef
6.
Zurück zum Zitat Fu, Y., L. Maianu, B.R. Melbert, and W.T. Garvey. 2004. Facilitative glucose transporter gene expression in human lymphocytes, monocytes, and macrophages: a role for glut isoforms 1, 3, and 5 in the immune response and foam cell formation. Blood Cells Molecules & Diseases 32 (1): 182–190.CrossRef Fu, Y., L. Maianu, B.R. Melbert, and W.T. Garvey. 2004. Facilitative glucose transporter gene expression in human lymphocytes, monocytes, and macrophages: a role for glut isoforms 1, 3, and 5 in the immune response and foam cell formation. Blood Cells Molecules & Diseases 32 (1): 182–190.CrossRef
7.
Zurück zum Zitat Zhang, J., and Y. Li. 2014. Fibroblast growth factor 21, the endocrine FGF pathway and novel treatments for metabolic syndrome. Drug Discovery Today 5 (19): 579–589.CrossRef Zhang, J., and Y. Li. 2014. Fibroblast growth factor 21, the endocrine FGF pathway and novel treatments for metabolic syndrome. Drug Discovery Today 5 (19): 579–589.CrossRef
8.
Zurück zum Zitat Kharitonenkov, A., T.L. Shiyanova, A. Koester, A.M. Ford, R. Micanovic, E.J. Galbreath, G.E. Sandusky, L.J. Hammond, J.S. Moyers, R.A. Owens, et al. 2005. FGF-21 as a novel metabolic regulator. The Journal of Clinical Investigation 115 (6): 1627–1635.CrossRefPubMedPubMedCentral Kharitonenkov, A., T.L. Shiyanova, A. Koester, A.M. Ford, R. Micanovic, E.J. Galbreath, G.E. Sandusky, L.J. Hammond, J.S. Moyers, R.A. Owens, et al. 2005. FGF-21 as a novel metabolic regulator. The Journal of Clinical Investigation 115 (6): 1627–1635.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Wang, W.F., L. Ma, M.Y. Liu, et al. 2015. A novel function for fibroblast growth factor 21: stimulation of NADPH oxidase-dependent ROS generation. Endocrine 49 (2): 1–11. Wang, W.F., L. Ma, M.Y. Liu, et al. 2015. A novel function for fibroblast growth factor 21: stimulation of NADPH oxidase-dependent ROS generation. Endocrine 49 (2): 1–11.
10.
Zurück zum Zitat Feingold, Kenneth R., Carl Grunfeld, Josef G. Heuer, Akanksha Gupta, Martin Cramer, Tonghai Zhang, et al. 2012. FGF21 is increased by inflammatory stimuli and protects leptin-deficient ob/ob mice from the toxicity of sepsis. Endocrinology 153 (6): 2689–2700.CrossRefPubMedPubMedCentral Feingold, Kenneth R., Carl Grunfeld, Josef G. Heuer, Akanksha Gupta, Martin Cramer, Tonghai Zhang, et al. 2012. FGF21 is increased by inflammatory stimuli and protects leptin-deficient ob/ob mice from the toxicity of sepsis. Endocrinology 153 (6): 2689–2700.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Izumiya, Y., H.A. Bina, N. Ouchi, Y. Akasaki, A. Kharitonenkov, and K. Walsh. 2008. FGF21 is an Akt-regulated myokine. FEBS Letters 582 (27): 3805–3810.CrossRefPubMedPubMedCentral Izumiya, Y., H.A. Bina, N. Ouchi, Y. Akasaki, A. Kharitonenkov, and K. Walsh. 2008. FGF21 is an Akt-regulated myokine. FEBS Letters 582 (27): 3805–3810.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Tanimura, Y., W. Aoi, Y. Takanami, et al. 2016. Acute exercise increases fibroblast growth factor 21 in metabolic organs and circulation. Physiological Reports 4 (12): e12828.CrossRefPubMedPubMedCentral Tanimura, Y., W. Aoi, Y. Takanami, et al. 2016. Acute exercise increases fibroblast growth factor 21 in metabolic organs and circulation. Physiological Reports 4 (12): e12828.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Arkan, M.C., A.L. Hevener, F.R. Greten, et al. 2005. IKK-β links inflammation to obesity-induced insulin resistance. Nature Medicine 11 (2): 191–198.CrossRefPubMed Arkan, M.C., A.L. Hevener, F.R. Greten, et al. 2005. IKK-β links inflammation to obesity-induced insulin resistance. Nature Medicine 11 (2): 191–198.CrossRefPubMed
14.
Zurück zum Zitat Lee, J.S., W.M. Nauseef, A. Moeenrezakhanlou, L.M. Sly, S. Noubir, K.G. Leidal, J.M. Schlomann, G. Krystal, and N.E. Reiner. 2007. Monocyte p110α phosphatidylinositol 3-kinase regulates phagocytosis, the phagocyte oxidase, and cytokine production. Journal of Leukocyte Biology 81: 1548–1561.CrossRefPubMed Lee, J.S., W.M. Nauseef, A. Moeenrezakhanlou, L.M. Sly, S. Noubir, K.G. Leidal, J.M. Schlomann, G. Krystal, and N.E. Reiner. 2007. Monocyte p110α phosphatidylinositol 3-kinase regulates phagocytosis, the phagocyte oxidase, and cytokine production. Journal of Leukocyte Biology 81: 1548–1561.CrossRefPubMed
15.
Zurück zum Zitat Guha, M., and N. Mackman. 2002. The phosphatidylinositol 3-kinase-Akt pathway limits lipopolysaccharide activation of signaling pathways and expression of inflammatory mediators in human monocytic cells. The Journal of Biological Chemistry 277: 32124–32132.CrossRefPubMed Guha, M., and N. Mackman. 2002. The phosphatidylinositol 3-kinase-Akt pathway limits lipopolysaccharide activation of signaling pathways and expression of inflammatory mediators in human monocytic cells. The Journal of Biological Chemistry 277: 32124–32132.CrossRefPubMed
17.
Zurück zum Zitat Lund, M.E., J. To, B.A. O'Brien, et al. 2016. The choice of phorbol 12-myristate 13-acetate differentiation protocol influences the response of THP-1 macrophages to a pro-inflammatory stimulus. Journal of Immunological Methods 430: 64–70.CrossRefPubMed Lund, M.E., J. To, B.A. O'Brien, et al. 2016. The choice of phorbol 12-myristate 13-acetate differentiation protocol influences the response of THP-1 macrophages to a pro-inflammatory stimulus. Journal of Immunological Methods 430: 64–70.CrossRefPubMed
18.
Zurück zum Zitat Auwerx, J. 1991. The human leukemia cell line, THP-1: a multifacetted model for the study of monocyte-macrophage differentiation. Experientia 47 (1): 22–31.CrossRefPubMed Auwerx, J. 1991. The human leukemia cell line, THP-1: a multifacetted model for the study of monocyte-macrophage differentiation. Experientia 47 (1): 22–31.CrossRefPubMed
19.
Zurück zum Zitat Millet, P., V. Vachharajani, L. McPhail, et al. 2016. GAPDH binding to TNF-α mRNA contributes to posttranscriptional repression in monocytes: a novel mechanism of communication between inflammation and metabolism. The Journal of Immunology 196 (6): 2541–2551.CrossRefPubMedPubMedCentral Millet, P., V. Vachharajani, L. McPhail, et al. 2016. GAPDH binding to TNF-α mRNA contributes to posttranscriptional repression in monocytes: a novel mechanism of communication between inflammation and metabolism. The Journal of Immunology 196 (6): 2541–2551.CrossRefPubMedPubMedCentral
Metadaten
Titel
FGF-21 Plays a Crucial Role in the Glucose Uptake of Activated Monocytes
verfasst von
Nan Wang
Jun-Yan Li
Ting-ting Zhao
Si-ming Li
Cheng-Bin Shen
De-Shan Li
Wen-Fei Wang
Publikationsdatum
30.09.2017
Verlag
Springer US
Erschienen in
Inflammation / Ausgabe 1/2018
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-017-0665-7

Weitere Artikel der Ausgabe 1/2018

Inflammation 1/2018 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.