POMC neurons expressing leptin receptors coordinate metabolic responses to fasting via suppression of leptin levels

Autor: Carlos M. Castorena, Heather M Dungan Lemko, Alexandre Caron, Syann Lee, Newaz Ahmed, Chen Liu, Charlotte E. Lee, Caleb C. Lord, Joel K. Elmquist, William L. Holland, Teppei Fujikawa
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Food intake
Sympathetic nervous system
Pro-Opiomelanocortin
Sympathetic Nervous System
Mouse
Glucose homeostasis
Eating
Mice
Homeostasis
Biology (General)
Neurons
General Neuroscience
Leptin
digestive
oral
and skin physiology
POMC
General Medicine
medicine.anatomical_structure
Receptors
Leptin
Medicine
hormones
hormone substitutes
and hormone antagonists
Research Article
medicine.medical_specialty
Adrenergic receptor
fasting
QH301-705.5
Science
Biology
Inhibitory postsynaptic potential
ADRA2A
leptin
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Receptors
Adrenergic
alpha-2
Internal medicine
medicine
Animals
Humans
Secretion
Human Biology and Medicine
Leptin receptor
General Immunology and Microbiology
030104 developmental biology
Endocrinology
Glucose
nervous system
Energy Metabolism
Neuroscience
Zdroj: eLife, Vol 7 (2018)
eLife
Popis: Leptin is critical for energy balance, glucose homeostasis, and for metabolic and neuroendocrine adaptations to starvation. A prevalent model predicts that leptin’s actions are mediated through pro-opiomelanocortin (POMC) neurons that express leptin receptors (LEPRs). However, previous studies have used prenatal genetic manipulations, which may be subject to developmental compensation. Here, we tested the direct contribution of POMC neurons expressing LEPRs in regulating energy balance, glucose homeostasis and leptin secretion during fasting using a spatiotemporally controlledLeprexpression mouse model. We report a dissociation between leptin’s effects on glucose homeostasis versus energy balance in POMC neurons. We show that these neurons are dispensable for regulating food intake, but are required for coordinating hepatic glucose production and for the fasting-induced fall in leptin levels, independent of changes in fat mass. We also identify a role for sympathetic nervous system regulation of the inhibitory adrenergic receptor (ADRA2A) in regulating leptin production. Collectively, our findings highlight a previously unrecognized role of POMC neurons in regulating leptin levels.
Databáze: OpenAIRE
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