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The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis

Glucose homeostasis can be improved after bariatric surgery, which alters bile flow and stimulates gut hormone secretion, particularly FGF15/19. FGFR1 expression in AGRP-expressing cells is required for bile acids’ ability to improve glucose control. We show that the mouse Agrp gene has 3 promoter/e...

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Autores principales: Liu, Shun-Mei, Ifebi, Bruno, Johnson, Fred, Xu, Alison, Ho, Jacquelin, Yang, Yunlei, Schwartz, Gary, Jo, Young Hwan, Chua, Streamson
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10065075/
https://www.ncbi.nlm.nih.gov/pubmed/36787185
http://dx.doi.org/10.1172/JCI164185
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author Liu, Shun-Mei
Ifebi, Bruno
Johnson, Fred
Xu, Alison
Ho, Jacquelin
Yang, Yunlei
Schwartz, Gary
Jo, Young Hwan
Chua, Streamson
author_facet Liu, Shun-Mei
Ifebi, Bruno
Johnson, Fred
Xu, Alison
Ho, Jacquelin
Yang, Yunlei
Schwartz, Gary
Jo, Young Hwan
Chua, Streamson
author_sort Liu, Shun-Mei
collection PubMed
description Glucose homeostasis can be improved after bariatric surgery, which alters bile flow and stimulates gut hormone secretion, particularly FGF15/19. FGFR1 expression in AGRP-expressing cells is required for bile acids’ ability to improve glucose control. We show that the mouse Agrp gene has 3 promoter/enhancer regions that direct transcription of each of their own AGRP transcripts. One of these Agrp promoters/enhancers, Agrp-B, is regulated by bile acids. We generated an Agrp-B knockin FLP/knockout allele. AGRP-B–expressing cells are found in endocrine cells of the pars tuberalis and coexpress diacylglycerol lipase B — an endocannabinoid biosynthetic enzyme — distinct from pars tuberalis thyrotropes. AGRP-B expression is also found in the folliculostellate cells of the pituitary’s anterior lobe. Mice without AGRP-B were protected from glucose intolerance induced by high-fat feeding but not from excess weight gain. Chemogenetic inhibition of AGRP-B cells improved glucose tolerance by enhancing glucose-stimulated insulin secretion. Inhibition of the AGRP-B cells also caused weight loss. The improved glucose tolerance and reduced body weight persisted up to 6 weeks after cessation of the DREADD-mediated inhibition, suggesting the presence of a biological switch for glucose homeostasis that is regulated by long-term stability of food availability.
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spelling pubmed-100650752023-04-03 The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis Liu, Shun-Mei Ifebi, Bruno Johnson, Fred Xu, Alison Ho, Jacquelin Yang, Yunlei Schwartz, Gary Jo, Young Hwan Chua, Streamson J Clin Invest Research Article Glucose homeostasis can be improved after bariatric surgery, which alters bile flow and stimulates gut hormone secretion, particularly FGF15/19. FGFR1 expression in AGRP-expressing cells is required for bile acids’ ability to improve glucose control. We show that the mouse Agrp gene has 3 promoter/enhancer regions that direct transcription of each of their own AGRP transcripts. One of these Agrp promoters/enhancers, Agrp-B, is regulated by bile acids. We generated an Agrp-B knockin FLP/knockout allele. AGRP-B–expressing cells are found in endocrine cells of the pars tuberalis and coexpress diacylglycerol lipase B — an endocannabinoid biosynthetic enzyme — distinct from pars tuberalis thyrotropes. AGRP-B expression is also found in the folliculostellate cells of the pituitary’s anterior lobe. Mice without AGRP-B were protected from glucose intolerance induced by high-fat feeding but not from excess weight gain. Chemogenetic inhibition of AGRP-B cells improved glucose tolerance by enhancing glucose-stimulated insulin secretion. Inhibition of the AGRP-B cells also caused weight loss. The improved glucose tolerance and reduced body weight persisted up to 6 weeks after cessation of the DREADD-mediated inhibition, suggesting the presence of a biological switch for glucose homeostasis that is regulated by long-term stability of food availability. American Society for Clinical Investigation 2023-04-03 /pmc/articles/PMC10065075/ /pubmed/36787185 http://dx.doi.org/10.1172/JCI164185 Text en © 2023 Liu et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Liu, Shun-Mei
Ifebi, Bruno
Johnson, Fred
Xu, Alison
Ho, Jacquelin
Yang, Yunlei
Schwartz, Gary
Jo, Young Hwan
Chua, Streamson
The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis
title The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis
title_full The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis
title_fullStr The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis
title_full_unstemmed The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis
title_short The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis
title_sort gut signals to agrp-expressing cells of the pituitary to control glucose homeostasis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10065075/
https://www.ncbi.nlm.nih.gov/pubmed/36787185
http://dx.doi.org/10.1172/JCI164185
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