Hepatic glycogenolysis and hypometabolism induced by chemogenetic stimulation of C1 neurons.

Autor: Abe C; Department of Physiology, Gifu University Graduate School of Medicine, Gifu, Japan.; Preemptive Food Research Center (PFRC), Gifu University Institute for Advanced Study, Gifu, Japan., Katayama C; Department of Physiology, Gifu University Graduate School of Medicine, Gifu, Japan., Bazek M; Department of Physiology, Gifu University Graduate School of Medicine, Gifu, Japan., Ohbayashi K; Laboratory of Animal Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, Japan., Horii K; Department of Physiology, Gifu University Graduate School of Medicine, Gifu, Japan., Tanida M; Department of Physiology II, Kanazawa Medical University, Ishikawa, Japan., Nin F; Department of Physiology, Gifu University Graduate School of Medicine, Gifu, Japan., Iwasaki Y; Laboratory of Animal Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, Japan.
Jazyk: angličtina
Zdroj: The Journal of physiology [J Physiol] 2023 Jun; Vol. 601 (12), pp. 2293-2306. Date of Electronic Publication: 2023 May 11.
DOI: 10.1113/JP284319
Abstrakt: The precise regulation of blood glucose levels is indispensable for maintaining physiological functions. C1 neurons determine the outflow of the autonomic nervous and endocrine systems to maintain blood glucose levels in the body. In contrast, activation of C1 neurons induces a decrease in activity, suggesting that hypoactivity also participates in maintaining blood glucose levels. To examine this, we evaluated both glycogenolysis and hypometabolism induced by the selective activation of C1 neurons. We used Dbh Cre/0 mice expressing receptors for chemogenetic tools in C1 neurons, resulting from microinjection of the viral vector. C1 neurons were activated by intraperitoneal injection of clozapine N-oxide (CNO). The chemogenetic activation of C1 neurons significantly decreased body temperature, oxygen consumption and carbon dioxide production. On the other hand, blood glucose levels were increased by activation of C1 neurons 2 h after CNO administration, even in the fasting state. In this situation, an increase in glucagon and corticosterone levels was observed, while hepatic glycogen content decreased significantly. Plasma insulin levels were not changed by the activation of C1 neurons despite the increase in blood glucose level. Furthermore, adrenal sympathetic nerve activity was significantly increased by the activation of C1 neurons, and plasma catecholamine levels increased significantly. In conclusion, the selective activation of C1 neurons using chemogenetic tools induced an increase in blood glucose levels, probably as a result of hepatic glycogenolysis and hypometabolism. KEY POINTS: Chemogenetic activation of C1 neurons in medulla oblongata decreased body temperature. Oxygen consumption and carbon dioxide production were decreased by chemogenetic activation of C1 neurons in medulla oblongata. Blood glucose levels were increased by chemogenetic activation of C1 neurons in medulla oblongata. Chemogenetic activation of C1 neurons in medulla oblongata increased glucagon, corticosterone and catecholamine levels in plasma. An increase in blood glucose levels by activation of C1 neurons occurred due to the combined effect of hepatic glycogenolysis and hypometabolism.
(© 2023 The Authors. The Journal of Physiology © 2023 The Physiological Society.)
Databáze: MEDLINE
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