Optogenetic stimulation of the liver-projecting melanocortinergic pathway promotes hepatic glucose production
| Autor: | Shun Mei Liu, Hye Young Joung, Eunjin Kwon, Gary J. Schwartz, Streamson C. Chua, Young Hwan Jo |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Blood Glucose
Male 0301 basic medicine Pro-Opiomelanocortin Action Potentials General Physics and Astronomy Mice 0302 clinical medicine Insulin Glucose homeostasis Multidisciplinary Chemistry digestive oral and skin physiology Vagus Nerve Cholinergic Neurons Up-Regulation medicine.anatomical_structure Liver Hypothalamus Gene Knockdown Techniques Receptor Melanocortin Type 4 Female Melanocortin hormones hormone substitutes and hormone antagonists Acetylcholine medicine.drug endocrine system medicine.medical_specialty Science Neurophysiology Efferent Pathways Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Central melanocortin system Arcuate nucleus Internal medicine medicine Animals Humans Autonomic nervous system RNA Messenger Arcuate Nucleus of Hypothalamus Gluconeogenesis General Chemistry Glucagon Hypoglycemia Optogenetics Disease Models Animal Metabolism 030104 developmental biology Endocrinology Dorsal motor nucleus nervous system Neuron Corticosterone 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020) |
| ISSN: | 2041-1723 |
| Popis: | The central melanocortin system plays a fundamental role in the control of feeding and body weight. Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC) also regulate overall glucose homeostasis via insulin-dependent and -independent pathways. Here, we report that a subset of ARC POMC neurons innervate the liver via preganglionic parasympathetic acetylcholine (ACh) neurons in the dorsal motor nucleus of the vagus (DMV). Optogenetic stimulation of this liver-projecting melanocortinergic pathway elevates blood glucose levels that is associated with increased expression of hepatic gluconeogenic enzymes in female and male mice. Pharmacological blockade and knockdown of the melanocortin-4 receptor gene in the DMV abolish this stimulation-induced effect. Activation of melanocortin-4 receptors inhibits DMV cholinergic neurons and optogenetic inhibition of liver-projecting parasympathetic cholinergic fibers increases blood glucose levels. This elevated blood glucose is not due to altered pancreatic hormone release. Interestingly, insulin-induced hypoglycemia increases ARC POMC neuron activity. Hence, this liver-projecting melanocortinergic circuit that we identified may play a critical role in the counterregulatory response to hypoglycemia. Hypothalamic melanocortin neurons regulate systemic glucose homeostasis through incompletely understood pathways. Here, the authors show that a subset of pro-opiomelanocortin neurons innervate the liver via preganglionic parasympathetic cholinergic neurons in the dorsal motor nucleus of the vagus and that stimulation of this pathway elevates blood glucose levels |
| Databáze: | OpenAIRE |
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