Journal article
Activation of Amygdala Prokineticin receptor 2 neurons drives the anorexigenic activity of the neuropeptide PK2
The Journal of biological chemistry, Vol.299(1), 102814
2023
DOI: 10.1016/j.jbc.2022.102814
PMCID: PMC9860486
PMID: 36539034
Abstract
Energy homeostasis is a complex system involving multiple hormones, neuropeptides, and receptors. Prokineticins (PK1 and PK2) are agonists to two G protein–coupled receptors, prokineticin receptor 1 and 2 (PKR1 and PKR2), which decrease food intake when injected in rodents. The relative contribution of PKR1 and PKR2 to the anorexigenic effect of PK2 and their site of action in the brain have not yet been elucidated. While PKR1 and PKR2 are both expressed in the hypothalamus, a central region involved in the control of energy homeostasis, PKR2 is also present in the amygdala, which has recently been shown to regulate food intake in response to several anorexigenic signals. PKR trafficking and signaling are inhibited by the melanocortin receptor accessory protein 2 (MRAP2), thus suggesting that MRAP2 has the potential to alter the anorexigenic activity of PK2 in vivo. In this study, we investigated the importance of PKR1 and PKR2 for PK2-mediated inhibition of food intake, the brain region involved in this function, and the effect of MRAP2 on PK2 action in vivo. Using targeted silencing of PKR2 and chemogenetic manipulation of PKR2 neurons, we show that the anorexigenic effect of PK2 is mediated by PKR2 in the amygdala and that altering MRAP2 expression in PKR2 neurons modulates the activity of PK2. Collectively, our results provide evidence that inhibition of food intake by PKs is not mediated through activation of hypothalamic neurons but rather amygdala PKR2 neurons and further establishes the importance of MRAP2 in the regulation of energy homeostasis.
Details
- Title: Subtitle
- Activation of Amygdala Prokineticin receptor 2 neurons drives the anorexigenic activity of the neuropeptide PK2
- Creators
- Terry C. YinAyushi MittalPaul BuscagliaWenxian LiJulien A. Sebag
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.299(1), 102814
- DOI
- 10.1016/j.jbc.2022.102814
- PMID
- 36539034
- PMCID
- PMC9860486
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Grant note
- DOI: 10.13039/100000002, name: NIH
- Language
- English
- Electronic publication date
- 12/2022
- Date published
- 2023
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Otolaryngology
- Record Identifier
- 9984333159402771
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