Deciphering an AgRP-serotoninergic neural circuit in distinct control of energy metabolism from feeding

Autor: István Tóth, Guobin Xia, Miao-Hsueh Chen, Giang Hoang, Monica Farias, Marcelo O. Dietrich, Dollada Srisai, Fan-Tao Meng, Yong Han, Yang He, Qi Wu, Yanlin He, Yali Ran, Yong Xu
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Serotonin
Bioenergetics
Science
Hypothalamus
Neural Conduction
Neurophysiology
General Physics and Astronomy
Optogenetics
Biology
Serotonergic
Neural circuits
Article
General Biochemistry
Genetics and Molecular Biology
Eating
Mice
03 medical and health sciences
0302 clinical medicine
Dorsal raphe nucleus
Adipose Tissue
Brown
Tandem Mass Spectrometry
Animals
Agouti-Related Protein
Obesity
Receptor
Multidisciplinary
digestive
oral
and skin physiology
Body Weight
Temperature
General Chemistry
Adipose Tissue
Beige
Melanocortin 4 receptor
Electrophysiology
Metabolism
030104 developmental biology
nervous system
Receptor
Melanocortin
Type 4
Melanocortin
Energy Metabolism
Neuroscience
030217 neurology & neurosurgery
Chromatography
Liquid
Serotonergic Neurons
Signal Transduction
Zdroj: Nature Communications
Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021)
ISSN: 2041-1723
DOI: 10.1038/s41467-021-23846-x
Popis: Contrasting to the established role of the hypothalamic agouti-related protein (AgRP) neurons in feeding regulation, the neural circuit and signaling mechanisms by which they control energy expenditure remains unclear. Here, we report that energy expenditure is regulated by a subgroup of AgRP neurons that send non-collateral projections to neurons within the dorsal lateral part of dorsal raphe nucleus (dlDRN) expressing the melanocortin 4 receptor (MC4R), which in turn innervate nearby serotonergic (5-HT) neurons. Genetic manipulations reveal a bi-directional control of energy expenditure by this circuit without affecting food intake. Fiber photometry and electrophysiological results indicate that the thermo-sensing MC4RdlDRN neurons integrate pre-synaptic AgRP signaling, thereby modulating the post-synaptic serotonergic pathway. Specifically, the MC4RdlDRN signaling elicits profound, bi-directional, regulation of body weight mainly through sympathetic outflow that reprograms mitochondrial bioenergetics within brown and beige fat while feeding remains intact. Together, we suggest that this AgRP neural circuit plays a unique role in persistent control of energy expenditure and body weight, hinting next-generation therapeutic approaches for obesity and metabolic disorders.
Neuronal signaling has an important role in the regulation of energy expenditure and body weight, however, the underlying mechanisms are incompletely understood. Here, the authors report a AgRP-MC4R-serotonin expressing neuronal circuit that regulate energy expenditure without affecting feeding.
Databáze: OpenAIRE
Externí odkaz: