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The gut hormone receptor GIPR links energy availability to the control of hematopoiesis

OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) conveys information from ingested nutrients to peripheral tissues, signaling energy availability. The GIP Receptor (GIPR) is also expressed in the bone marrow, notably in cells of the myeloid lineage. However, the importance of gain and l...

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Autores principales: Pujadas, Gemma, Varin, Elodie M., Baggio, Laurie L., Mulvihill, Erin E., Bang, K.W.Annie, Koehler, Jacqueline A., Matthews, Dianne, Drucker, Daniel J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283165/
https://www.ncbi.nlm.nih.gov/pubmed/32389828
http://dx.doi.org/10.1016/j.molmet.2020.101008
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author Pujadas, Gemma
Varin, Elodie M.
Baggio, Laurie L.
Mulvihill, Erin E.
Bang, K.W.Annie
Koehler, Jacqueline A.
Matthews, Dianne
Drucker, Daniel J.
author_facet Pujadas, Gemma
Varin, Elodie M.
Baggio, Laurie L.
Mulvihill, Erin E.
Bang, K.W.Annie
Koehler, Jacqueline A.
Matthews, Dianne
Drucker, Daniel J.
author_sort Pujadas, Gemma
collection PubMed
description OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) conveys information from ingested nutrients to peripheral tissues, signaling energy availability. The GIP Receptor (GIPR) is also expressed in the bone marrow, notably in cells of the myeloid lineage. However, the importance of gain and loss of GIPR signaling for diverse hematopoietic responses remains unclear. METHODS: We assessed the expression of the Gipr in bone marrow (BM) lineages and examined functional roles for the GIPR in control of hematopoiesis. Bone marrow responses were studied in (i) mice fed regular or energy-rich diets, (ii) mice treated with hematopoietic stressors including acute 5-fluorouracil (5-FU), pamsaccharide (LPS), and Pam3CysSerLys4 (Pam3CSK4), with or without pharmacological administration of a GIPR agonist, and (iii) mice with global (Gipr(−/−)) or selective deletion of the GIPR (Gipr(Tie2−/−)) with and without bone marrow transplantation (BMT). RESULTS: Gipr is expressed within T cells, myeloid cells, and myeloid precursors; however, these cell populations were not different in peripheral blood, spleen, or BM of Gipr(−/−) and Gipr(Tie2−/−) mice. Nevertheless, gain and loss of function studies revealed that GIPR signaling controls the expression of BM Toll-like receptor (TLR) and Notch-related genes regulating hematopoiesis. Loss of the BM GIPR attenuates the extent of adipose tissue inflammation and dysregulates the hematopoietic response to BMT. GIPR agonism modified BM gene expression profiles following 5-FU and Pam3CSK4 whereas loss of the Gipr altered the hematopoietic responses to energy excess, two TLR ligands, and 5-FU. However, the magnitude of the cellular changes in hematopoiesis in response to gain or loss of GIPR signaling was relatively modest. CONCLUSION: These studies identify a functional gut hormone-BM axis positioned for the transduction of signals linking nutrient availability to the control of TLR and Notch genes regulating hematopoiesis. Nevertheless, stimulation or loss of GIPR signaling has minimal impact on basal hematopoiesis or the physiological response to hematopoietic stress.
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spelling pubmed-72831652020-06-10 The gut hormone receptor GIPR links energy availability to the control of hematopoiesis Pujadas, Gemma Varin, Elodie M. Baggio, Laurie L. Mulvihill, Erin E. Bang, K.W.Annie Koehler, Jacqueline A. Matthews, Dianne Drucker, Daniel J. Mol Metab Original Article OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) conveys information from ingested nutrients to peripheral tissues, signaling energy availability. The GIP Receptor (GIPR) is also expressed in the bone marrow, notably in cells of the myeloid lineage. However, the importance of gain and loss of GIPR signaling for diverse hematopoietic responses remains unclear. METHODS: We assessed the expression of the Gipr in bone marrow (BM) lineages and examined functional roles for the GIPR in control of hematopoiesis. Bone marrow responses were studied in (i) mice fed regular or energy-rich diets, (ii) mice treated with hematopoietic stressors including acute 5-fluorouracil (5-FU), pamsaccharide (LPS), and Pam3CysSerLys4 (Pam3CSK4), with or without pharmacological administration of a GIPR agonist, and (iii) mice with global (Gipr(−/−)) or selective deletion of the GIPR (Gipr(Tie2−/−)) with and without bone marrow transplantation (BMT). RESULTS: Gipr is expressed within T cells, myeloid cells, and myeloid precursors; however, these cell populations were not different in peripheral blood, spleen, or BM of Gipr(−/−) and Gipr(Tie2−/−) mice. Nevertheless, gain and loss of function studies revealed that GIPR signaling controls the expression of BM Toll-like receptor (TLR) and Notch-related genes regulating hematopoiesis. Loss of the BM GIPR attenuates the extent of adipose tissue inflammation and dysregulates the hematopoietic response to BMT. GIPR agonism modified BM gene expression profiles following 5-FU and Pam3CSK4 whereas loss of the Gipr altered the hematopoietic responses to energy excess, two TLR ligands, and 5-FU. However, the magnitude of the cellular changes in hematopoiesis in response to gain or loss of GIPR signaling was relatively modest. CONCLUSION: These studies identify a functional gut hormone-BM axis positioned for the transduction of signals linking nutrient availability to the control of TLR and Notch genes regulating hematopoiesis. Nevertheless, stimulation or loss of GIPR signaling has minimal impact on basal hematopoiesis or the physiological response to hematopoietic stress. Elsevier 2020-05-07 /pmc/articles/PMC7283165/ /pubmed/32389828 http://dx.doi.org/10.1016/j.molmet.2020.101008 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Pujadas, Gemma
Varin, Elodie M.
Baggio, Laurie L.
Mulvihill, Erin E.
Bang, K.W.Annie
Koehler, Jacqueline A.
Matthews, Dianne
Drucker, Daniel J.
The gut hormone receptor GIPR links energy availability to the control of hematopoiesis
title The gut hormone receptor GIPR links energy availability to the control of hematopoiesis
title_full The gut hormone receptor GIPR links energy availability to the control of hematopoiesis
title_fullStr The gut hormone receptor GIPR links energy availability to the control of hematopoiesis
title_full_unstemmed The gut hormone receptor GIPR links energy availability to the control of hematopoiesis
title_short The gut hormone receptor GIPR links energy availability to the control of hematopoiesis
title_sort gut hormone receptor gipr links energy availability to the control of hematopoiesis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283165/
https://www.ncbi.nlm.nih.gov/pubmed/32389828
http://dx.doi.org/10.1016/j.molmet.2020.101008
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