Abstract
The melanocortin-3 receptor (MC3R) is a negative regulator of the central melanocortin circuitry via presynaptic expression on agouti-related protein (AgRP) nerve terminals, from where it regulates GABA release onto secondary MC4R-expressing neurons. However, MC3R knockout (KO) mice also exhibit defective behavioral and neuroendocrine responses to fasting. Here, we demonstrate that MC3R KO mice exhibit defective activation of AgRP neurons in response to fasting, cold exposure, or ghrelin while exhibiting normal inhibition of AgRP neurons by sensory detection of food in the ad libitum-fed state. Using a conditional MC3R KO model, we show that the control of AgRP neuron activation by fasting and ghrelin requires the specific presence of MC3R within AgRP neurons. Thus, MC3R is a crucial player in the responsiveness of the AgRP soma to both hormonal and neuronal signals of energy need.
Original language | English (US) |
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Article number | 113188 |
Journal | Cell Reports |
Volume | 42 |
Issue number | 10 |
DOIs | |
State | Published - Oct 31 2023 |
Keywords
- AgRP
- CP: Metabolism
- CP: Neuroscience
- fasting
- food intake
- ghrelin
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology