Granulocyte colony-stimulating factor (G-CSF): A saturated fatty acid-induced myokine with insulin-desensitizing properties in humans
Objective: Circulating long-chain free fatty acids (FFAs) are important metabolic signals that acutely enhance fatty acid oxidation, thermogenesis, energy expenditure, and insulin secretion. However, if chronically elevated, they provoke inflammation, insulin resistance, and β-cell failure. Moreover...
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Format: | Article |
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Elsevier
2016-04-01
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Series: | Molecular Metabolism |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877816000235 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anna-Maria Ordelheide Nadja Gommer Anja Böhm Carina Hermann Inga Thielker Fausto Machicao Andreas Fritsche Norbert Stefan Hans-Ulrich Häring Harald Staiger |
spellingShingle |
Anna-Maria Ordelheide Nadja Gommer Anja Böhm Carina Hermann Inga Thielker Fausto Machicao Andreas Fritsche Norbert Stefan Hans-Ulrich Häring Harald Staiger Granulocyte colony-stimulating factor (G-CSF): A saturated fatty acid-induced myokine with insulin-desensitizing properties in humans Molecular Metabolism |
author_facet |
Anna-Maria Ordelheide Nadja Gommer Anja Böhm Carina Hermann Inga Thielker Fausto Machicao Andreas Fritsche Norbert Stefan Hans-Ulrich Häring Harald Staiger |
author_sort |
Anna-Maria Ordelheide |
title |
Granulocyte colony-stimulating factor (G-CSF): A saturated fatty acid-induced myokine with insulin-desensitizing properties in humans |
title_short |
Granulocyte colony-stimulating factor (G-CSF): A saturated fatty acid-induced myokine with insulin-desensitizing properties in humans |
title_full |
Granulocyte colony-stimulating factor (G-CSF): A saturated fatty acid-induced myokine with insulin-desensitizing properties in humans |
title_fullStr |
Granulocyte colony-stimulating factor (G-CSF): A saturated fatty acid-induced myokine with insulin-desensitizing properties in humans |
title_full_unstemmed |
Granulocyte colony-stimulating factor (G-CSF): A saturated fatty acid-induced myokine with insulin-desensitizing properties in humans |
title_sort |
granulocyte colony-stimulating factor (g-csf): a saturated fatty acid-induced myokine with insulin-desensitizing properties in humans |
publisher |
Elsevier |
series |
Molecular Metabolism |
issn |
2212-8778 |
publishDate |
2016-04-01 |
description |
Objective: Circulating long-chain free fatty acids (FFAs) are important metabolic signals that acutely enhance fatty acid oxidation, thermogenesis, energy expenditure, and insulin secretion. However, if chronically elevated, they provoke inflammation, insulin resistance, and β-cell failure. Moreover, FFAs act via multiple signaling pathways as very potent regulators of gene expression. In human skeletal muscle cells differentiated in vitro (myotubes), we have shown in previous studies that the expression of CSF3, the gene encoding granulocyte colony-stimulating factor (G-CSF), is markedly induced upon FFA treatment and exercise. Methods and results: We now report that CSF3 is induced in human myotubes by saturated, but not unsaturated, FFAs via Toll-like receptor 4-dependent and -independent pathways including activation of Rel-A, AP-1, C/EBPα, Src, and stress kinases. Furthermore, we show that human adipocytes and myotubes treated with G-CSF become insulin-resistant. In line with this, a functional polymorphism in the CSF3 gene affects adipose tissue- and whole-body insulin sensitivity and glucose tolerance in human subjects with elevated plasma FFA concentrations. Conclusion: G-CSF emerges as a new player in FFA-induced insulin resistance and thus may be of interest as a target for prevention and treatment of type 2 diabetes. Keywords: Granulocyte colony-stimulating factor (G-CSF), Saturated fatty acid-induced myokine, Fatty acid-induced insulin resistance |
url |
http://www.sciencedirect.com/science/article/pii/S2212877816000235 |
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doaj-32ee78b83d0544c6b5fb09013cd0f4a52020-11-25T00:49:55ZengElsevierMolecular Metabolism2212-87782016-04-0154305316Granulocyte colony-stimulating factor (G-CSF): A saturated fatty acid-induced myokine with insulin-desensitizing properties in humansAnna-Maria Ordelheide0Nadja Gommer1Anja Böhm2Carina Hermann3Inga Thielker4Fausto Machicao5Andreas Fritsche6Norbert Stefan7Hans-Ulrich Häring8Harald Staiger9Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Tübingen, GermanyDepartment of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Tübingen, Germany; Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Tübingen, Germany; Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany; Department of Internal Medicine, Division of Nutritional and Preventive Medicine, University Hospital Tübingen, Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Tübingen, Germany; Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Tübingen, Germany; Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Tübingen, Germany; Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany; Corresponding author. Internal Medicine IV, University Hospital Tübingen, Otfried-Müller-Str. 10, D-72076 Tübingen, Germany, Tel.: +49 7071 2985774; fax: +49 7071 295646.Objective: Circulating long-chain free fatty acids (FFAs) are important metabolic signals that acutely enhance fatty acid oxidation, thermogenesis, energy expenditure, and insulin secretion. However, if chronically elevated, they provoke inflammation, insulin resistance, and β-cell failure. Moreover, FFAs act via multiple signaling pathways as very potent regulators of gene expression. In human skeletal muscle cells differentiated in vitro (myotubes), we have shown in previous studies that the expression of CSF3, the gene encoding granulocyte colony-stimulating factor (G-CSF), is markedly induced upon FFA treatment and exercise. Methods and results: We now report that CSF3 is induced in human myotubes by saturated, but not unsaturated, FFAs via Toll-like receptor 4-dependent and -independent pathways including activation of Rel-A, AP-1, C/EBPα, Src, and stress kinases. Furthermore, we show that human adipocytes and myotubes treated with G-CSF become insulin-resistant. In line with this, a functional polymorphism in the CSF3 gene affects adipose tissue- and whole-body insulin sensitivity and glucose tolerance in human subjects with elevated plasma FFA concentrations. Conclusion: G-CSF emerges as a new player in FFA-induced insulin resistance and thus may be of interest as a target for prevention and treatment of type 2 diabetes. Keywords: Granulocyte colony-stimulating factor (G-CSF), Saturated fatty acid-induced myokine, Fatty acid-induced insulin resistancehttp://www.sciencedirect.com/science/article/pii/S2212877816000235 |