Exenatide administration time-dependently affects the hepatic circadian clock through glucagon-like peptide-1 receptors in the central nervous system.

Autor: Xu P; Department of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan., Morishige JI; Department of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan., Jing Z; Department of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan., Nagata N; Department of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan., Shi Y; Department of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan., Iba T; Department of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan., Daikoku T; Division of Animal Disease Model, Research Center for Experimental Modeling of Human Disease, Kanazawa University, Kanazawa, Japan., Ono M; Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo, Japan., Maida Y; Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan., Fujiwara T; Department of Human Life Environments, Kyoto Notre Dame University, Kyoto, Japan., Fujiwara H; Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan; Ochi Yume Clinic Nagoya, Nagoya, Japan., Ando H; Department of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan. Electronic address: h-ando@med.kanazawa-u.ac.jp.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2024 Dec; Vol. 230 (Pt 1), pp. 116567. Date of Electronic Publication: 2024 Oct 05.
DOI: 10.1016/j.bcp.2024.116567
Abstrakt: Accumulating evidence indicates that disruption of the circadian clock contributes to the development of lifestyle-related diseases. We have previously shown that exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, can strongly affect the molecular clocks in the peripheral tissues. This study aimed to investigate the effects of its dosing time and the central nervous system-specific GLP-1 receptor knockdown (GLP1RKD) on the hepatic clock in mice treated with exenatide. Male C57BL/6J and GLP1RKD mice were housed under a 12-h/12-h light/dark cycle, and feeding was restricted to either the light period (L-TRF) or the first 4 h in the dark period (D-TRF). In parallel, exenatide was administered 4-5 times, once daily either at the beginning of the dark (ZT 12) or light period (ZT 0), and we assessed the mRNA expression rhythms of clock genes in the liver thereafter. Exenatide administration at ZT 12 counteracted the phase shift effect of the L-TRF on the hepatic clock of wild-type mice, whereas the dosing at ZT 0 enhanced its effect. However, exenatide did not influence the phase of the hepatic clock under D-TRF regardless of the dosing time. The effect of exenatide in wild-type mice weakened in GLP1RKD mice. These results showed that exenatide dosing time-dependently affects the hepatic circadian clock through the central GLP-1 system. Exenatide administration at the beginning of the active period (i.e., in the morning for humans) might prevent disruption of the peripheral clocks caused by irregular eating habits.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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