Document Type
Article
Publication Date
12-1-2021
Abstract
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.
Recommended Citation
Han, Y., Xia, G., Srisai, D., Meng, F., He, Y., Ran, Y., He, Y., Farias, M., Hoang, G., Tóth, I., Dietrich, M., Chen, M., Xu, Y., & Wu, Q. (2021). Deciphering an AgRP-serotoninergic neural circuit in distinct control of energy metabolism from feeding. Retrieved from https://repository.lsu.edu/pbrc_basic_science_pubs/40