Circadian Clock Component BMAL1 in the Paraventricular Nucleus Regulates Glucose Metabolism

• Published in: Nutrients Vol. 13; no. 12; p. 4487
• Main Authors: Nakata, Masanori, Kumari, Parmila, Kita, Rika, Katsui, Nanako, Takeuchi, Yuriko, Kawaguchi, Tomoki, Yamazaki, Toshiya, Zhang, Boyang, Shimba, Shigeki, Yada, Toshihiko
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15-12-2021; MDPI
• Subjects: Animals; Arginine Vasopressin - genetics; Arginine Vasopressin - metabolism; Argipressin; ARNTL Transcription Factors - genetics; ARNTL Transcription Factors - metabolism; Beta cells; Biological clocks; BMAL1; BMAL1 protein; Brain; circadian; Circadian Clocks - physiology; Circadian rhythm; Circadian rhythms; Clock gene; Enzymes; Gene expression; Gene Expression Regulation - physiology; Glucose; Glucose - metabolism; Glucose Intolerance; Glucose tolerance; Homeostasis; Hypothalamus; Immunoassay; Insulin; Insulin - metabolism; insulin release; Insulin secretion; Lipid metabolism; Lipids; Metabolism; Mice; Mice, Knockout; Neurons; Neuropeptides; Obesity; Paraventricular Hypothalamic Nucleus - physiology; Paraventricular nucleus; Plasma; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Vasopressin; United States > US; Japan; insulin release; circadian; BMAL1; glucose metabolism; vasopressin; paraventricular nucleus
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu13124487

It is suggested that clock genes link the circadian rhythm to glucose and lipid metabolism. In this study, we explored the role of the clock gene
in the hypothalamic paraventricular nucleus (PVN) in glucose metabolism. The
-
-mediated deletion of
markedly reduced insulin secretion, resulting in impaired glucose tolerance. The pancreatic islets' responses to glucose, sulfonylureas (SUs) and arginine vasopressin (AVP) were well maintained. To specify the PVN neuron subpopulation targeted by Bmal1, the expression of neuropeptides was examined. In these knockout (KO) mice, the mRNA expression of
in the PVN was selectively decreased, and the plasma AVP concentration was also decreased. However, fasting suppressed
expression in both KO and Cre mice. These results demonstrate that PVN BMAL1 maintains
expression in the PVN and release to the circulation, possibly providing islet β-cells with more AVP. This action helps enhance insulin release and, consequently, glucose tolerance. In contrast, the circadian variation of
expression is regulated by feeding, but not by PVN BMAL1.