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Indirect Effects of Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 on the Peripheral Circadian Clocks in Mice

Circadian clocks in peripheral tissues are powerfully entrained by feeding. The mechanisms underlying this food entrainment remain unclear, although various humoral and neural factors have been reported to affect peripheral clocks. Because glucagon-like peptide-1 (GLP-1), which is rapidly secreted i...

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Autores principales: Ando, Hitoshi, Ushijima, Kentarou, Fujimura, Akio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829942/
https://www.ncbi.nlm.nih.gov/pubmed/24260546
http://dx.doi.org/10.1371/journal.pone.0081119
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author Ando, Hitoshi
Ushijima, Kentarou
Fujimura, Akio
author_facet Ando, Hitoshi
Ushijima, Kentarou
Fujimura, Akio
author_sort Ando, Hitoshi
collection PubMed
description Circadian clocks in peripheral tissues are powerfully entrained by feeding. The mechanisms underlying this food entrainment remain unclear, although various humoral and neural factors have been reported to affect peripheral clocks. Because glucagon-like peptide-1 (GLP-1), which is rapidly secreted in response to food ingestion, influences multiple humoral and neural signaling pathways, we suggest that GLP-1 plays a role in the food entrainment of peripheral clocks. To test this, we compared the effects of exendin-4, a GLP-1 receptor agonist, on mRNA expression of the clock genes (Clock, Bmal1, Nr1d1, Per1, Per2, and Cry1) with those of refeeding. In addition, we investigated whether exendin-4 could affect the rhythms of the peripheral clocks. In male C57BL/6J mice, although refeeding rapidly (within 2 h) altered mRNA levels of Per1 and Per2 in the liver and that of Per1 in adipose tissue, a single i.p. injection of exendin-4 did not cause such changes. However, unlike the GLP-1 receptor antagonist exendin-(9–39), exendin-4 significantly influenced Per1 mRNA levels in the liver at 12 h after injection. Moreover, pretreatment with exendin-4 affected the rapid-feeding-induced change in Per1 not only in the liver, but also in adipose tissue, without effect on food intake. Furthermore, during light-phase restricted feeding, repeated dosing of exendin-4 at the beginning of the dark phase profoundly influenced both the food intake and daily rhythms of clock gene expression in peripheral tissues. Thus, these results suggest that exendin-4 modulates peripheral clocks via multiple mechanisms different from those of refeeding.
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spelling pubmed-38299422013-11-20 Indirect Effects of Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 on the Peripheral Circadian Clocks in Mice Ando, Hitoshi Ushijima, Kentarou Fujimura, Akio PLoS One Research Article Circadian clocks in peripheral tissues are powerfully entrained by feeding. The mechanisms underlying this food entrainment remain unclear, although various humoral and neural factors have been reported to affect peripheral clocks. Because glucagon-like peptide-1 (GLP-1), which is rapidly secreted in response to food ingestion, influences multiple humoral and neural signaling pathways, we suggest that GLP-1 plays a role in the food entrainment of peripheral clocks. To test this, we compared the effects of exendin-4, a GLP-1 receptor agonist, on mRNA expression of the clock genes (Clock, Bmal1, Nr1d1, Per1, Per2, and Cry1) with those of refeeding. In addition, we investigated whether exendin-4 could affect the rhythms of the peripheral clocks. In male C57BL/6J mice, although refeeding rapidly (within 2 h) altered mRNA levels of Per1 and Per2 in the liver and that of Per1 in adipose tissue, a single i.p. injection of exendin-4 did not cause such changes. However, unlike the GLP-1 receptor antagonist exendin-(9–39), exendin-4 significantly influenced Per1 mRNA levels in the liver at 12 h after injection. Moreover, pretreatment with exendin-4 affected the rapid-feeding-induced change in Per1 not only in the liver, but also in adipose tissue, without effect on food intake. Furthermore, during light-phase restricted feeding, repeated dosing of exendin-4 at the beginning of the dark phase profoundly influenced both the food intake and daily rhythms of clock gene expression in peripheral tissues. Thus, these results suggest that exendin-4 modulates peripheral clocks via multiple mechanisms different from those of refeeding. Public Library of Science 2013-11-15 /pmc/articles/PMC3829942/ /pubmed/24260546 http://dx.doi.org/10.1371/journal.pone.0081119 Text en © 2013 Ando et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ando, Hitoshi
Ushijima, Kentarou
Fujimura, Akio
Indirect Effects of Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 on the Peripheral Circadian Clocks in Mice
title Indirect Effects of Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 on the Peripheral Circadian Clocks in Mice
title_full Indirect Effects of Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 on the Peripheral Circadian Clocks in Mice
title_fullStr Indirect Effects of Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 on the Peripheral Circadian Clocks in Mice
title_full_unstemmed Indirect Effects of Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 on the Peripheral Circadian Clocks in Mice
title_short Indirect Effects of Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 on the Peripheral Circadian Clocks in Mice
title_sort indirect effects of glucagon-like peptide-1 receptor agonist exendin-4 on the peripheral circadian clocks in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829942/
https://www.ncbi.nlm.nih.gov/pubmed/24260546
http://dx.doi.org/10.1371/journal.pone.0081119
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