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Physiological roles of the GIP receptor in murine brown adipose tissue
OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) is secreted from the gut in response to nutrient ingestion and promotes meal-dependent insulin secretion and lipid metabolism. Loss or attenuation of GIP receptor (GIPR) action leads to resistance to diet-induced obesity through incomplet...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822254/ https://www.ncbi.nlm.nih.gov/pubmed/31451430 http://dx.doi.org/10.1016/j.molmet.2019.08.006 |
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author | Beaudry, Jacqueline L. Kaur, Kiran D. Varin, Elodie M. Baggio, Laurie L. Cao, Xiemin Mulvihill, Erin E. Bates, Holly E. Campbell, Jonathan E. Drucker, Daniel J. |
author_facet | Beaudry, Jacqueline L. Kaur, Kiran D. Varin, Elodie M. Baggio, Laurie L. Cao, Xiemin Mulvihill, Erin E. Bates, Holly E. Campbell, Jonathan E. Drucker, Daniel J. |
author_sort | Beaudry, Jacqueline L. |
collection | PubMed |
description | OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) is secreted from the gut in response to nutrient ingestion and promotes meal-dependent insulin secretion and lipid metabolism. Loss or attenuation of GIP receptor (GIPR) action leads to resistance to diet-induced obesity through incompletely understood mechanisms. The GIPR is expressed in white adipose tissue; however, its putative role in brown adipose tissue (BAT) has not been explored. METHODS: We investigated the role of the GIPR in BAT cells in vitro and in BAT-specific (Gipr(BAT−/−)) knockout mice with selective elimination of the Gipr within the Myf5(+) expression domain. We analyzed body weight, adiposity, glucose homeostasis, insulin and lipid tolerance, energy expenditure, food intake, body temperature, and iBAT oxygen consumption ex vivo. High-fat diet (HFD)-fed Gipr(BAT−/−) mice were studied at room temperature (21 °C), 4 °C, and 30 °C ambient temperatures. RESULTS: The mouse Gipr gene is expressed in BAT, and GIP directly increased Il6 mRNA and IL-6 secretion in BAT cells. Additionally, levels of thermogenic, lipid and inflammation mRNA transcripts were altered in BAT cells transfected with Gipr siRNA. Body weight gain, energy expenditure, and glucose and insulin tolerance were normal in HFD-fed Gipr(BAT−/−) mice housed at room temperature. However, Gipr(BAT−/−) mice exhibited higher body temperatures during an acute cold challenge and a lower respiratory exchange ratio and impaired lipid tolerance at 21 °C. In contrast, body weight was lower and iBAT oxygen consumption was higher in HFD-fed mice housed at 4 °C but not at 30 °C. CONCLUSIONS: The BAT GIPR is linked to the control of metabolic gene expression, fuel utilization, and oxygen consumption. However, the selective loss of the GIPR within BAT is insufficient to recapitulate the findings of decreased weight gain and resistance to obesity arising in experimental models with systemic disruption of GIP action. |
format | Online Article Text |
id | pubmed-6822254 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-68222542019-11-06 Physiological roles of the GIP receptor in murine brown adipose tissue Beaudry, Jacqueline L. Kaur, Kiran D. Varin, Elodie M. Baggio, Laurie L. Cao, Xiemin Mulvihill, Erin E. Bates, Holly E. Campbell, Jonathan E. Drucker, Daniel J. Mol Metab Original Article OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) is secreted from the gut in response to nutrient ingestion and promotes meal-dependent insulin secretion and lipid metabolism. Loss or attenuation of GIP receptor (GIPR) action leads to resistance to diet-induced obesity through incompletely understood mechanisms. The GIPR is expressed in white adipose tissue; however, its putative role in brown adipose tissue (BAT) has not been explored. METHODS: We investigated the role of the GIPR in BAT cells in vitro and in BAT-specific (Gipr(BAT−/−)) knockout mice with selective elimination of the Gipr within the Myf5(+) expression domain. We analyzed body weight, adiposity, glucose homeostasis, insulin and lipid tolerance, energy expenditure, food intake, body temperature, and iBAT oxygen consumption ex vivo. High-fat diet (HFD)-fed Gipr(BAT−/−) mice were studied at room temperature (21 °C), 4 °C, and 30 °C ambient temperatures. RESULTS: The mouse Gipr gene is expressed in BAT, and GIP directly increased Il6 mRNA and IL-6 secretion in BAT cells. Additionally, levels of thermogenic, lipid and inflammation mRNA transcripts were altered in BAT cells transfected with Gipr siRNA. Body weight gain, energy expenditure, and glucose and insulin tolerance were normal in HFD-fed Gipr(BAT−/−) mice housed at room temperature. However, Gipr(BAT−/−) mice exhibited higher body temperatures during an acute cold challenge and a lower respiratory exchange ratio and impaired lipid tolerance at 21 °C. In contrast, body weight was lower and iBAT oxygen consumption was higher in HFD-fed mice housed at 4 °C but not at 30 °C. CONCLUSIONS: The BAT GIPR is linked to the control of metabolic gene expression, fuel utilization, and oxygen consumption. However, the selective loss of the GIPR within BAT is insufficient to recapitulate the findings of decreased weight gain and resistance to obesity arising in experimental models with systemic disruption of GIP action. Elsevier 2019-08-10 /pmc/articles/PMC6822254/ /pubmed/31451430 http://dx.doi.org/10.1016/j.molmet.2019.08.006 Text en © 2019 The Authors 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 Beaudry, Jacqueline L. Kaur, Kiran D. Varin, Elodie M. Baggio, Laurie L. Cao, Xiemin Mulvihill, Erin E. Bates, Holly E. Campbell, Jonathan E. Drucker, Daniel J. Physiological roles of the GIP receptor in murine brown adipose tissue |
title | Physiological roles of the GIP receptor in murine brown adipose tissue |
title_full | Physiological roles of the GIP receptor in murine brown adipose tissue |
title_fullStr | Physiological roles of the GIP receptor in murine brown adipose tissue |
title_full_unstemmed | Physiological roles of the GIP receptor in murine brown adipose tissue |
title_short | Physiological roles of the GIP receptor in murine brown adipose tissue |
title_sort | physiological roles of the gip receptor in murine brown adipose tissue |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822254/ https://www.ncbi.nlm.nih.gov/pubmed/31451430 http://dx.doi.org/10.1016/j.molmet.2019.08.006 |
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