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Published in: Inflammation 1/2018

01-02-2018 | ORIGINAL ARTICLE

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

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

Published in: Inflammation | Issue 1/2018

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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.
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Literature
1.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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.
go back to reference 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
Metadata
Title
FGF-21 Plays a Crucial Role in the Glucose Uptake of Activated Monocytes
Authors
Nan Wang
Jun-Yan Li
Ting-ting Zhao
Si-ming Li
Cheng-Bin Shen
De-Shan Li
Wen-Fei Wang
Publication date
01-02-2018
Publisher
Springer US
Published in
Inflammation / Issue 1/2018
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-017-0665-7

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