PMID- 37242151
OWN - NLM
STAT- MEDLINE
DCOM- 20230529
LR  - 20230529
IS  - 2072-6643 (Electronic)
IS  - 2072-6643 (Linking)
VI  - 15
IP  - 10
DP  - 2023 May 11
TI  - GPR-160 Receptor Signaling in the Dorsal Vagal Complex of Male Rats Modulates 
      Meal Microstructure and CART-Mediated Hypophagia.
LID - 10.3390/nu15102268 [doi]
LID - 2268
AB  - The g-protein coupled receptor GPR-160, recently identified as a putative 
      receptor for the cocaine and amphetamine-regulated transcript (CART) peptide, 
      shows abundant expression in the energy-balance control nuclei, including the 
      dorsal vagal complex (DVC). However, its physiological role in the control of 
      food intake has yet to be fully explored. Here, we performed a virally mediated, 
      targeted knockdown (KD) of Gpr160 in the DVC of male rats to evaluate its 
      physiological role in control of feeding. Our results indicate that DVC Gpr160 KD 
      affects meal microstructure. Specifically, DVC Gpr160 KD animals consumed more 
      frequent, but shorter meals during the dark phase and showed decreased caloric 
      intake and duration of meals during the light phase. Cumulatively, however, these 
      bidirectional effects on feeding resulted in no difference in body weight gain. 
      We next tested the role of DVC GPR-160 in mediating the anorexigenic effects of 
      exogenous CART. Our results show that DVC Gpr160 KD partially attenuates CART's 
      anorexigenic effects. To further characterize Gpr160+ cells in the DVC, we 
      utilized single-nucleus RNA sequencing data to uncover abundant GPR-160 
      expression in DVC microglia and only minimal expression in neurons. Altogether, 
      our results suggest that DVC CART signaling may be mediated by Gpr160+ microglia, 
      which in turn may be modulating DVC neuronal activity to control food intake.
FAU - Sanchez-Navarro, Marcos J
AU  - Sanchez-Navarro MJ
AUID- ORCID: 0000-0002-3099-788X
AD  - Department of Psychiatry, Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA 19104, USA.
FAU - Borner, Tito
AU  - Borner T
AD  - Department of Psychiatry, Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA 19104, USA.
FAU - Reiner, Benjamin C
AU  - Reiner BC
AUID- ORCID: 0000-0001-7796-587X
AD  - Department of Psychiatry, Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA 19104, USA.
FAU - Crist, Richard C
AU  - Crist RC
AD  - Department of Psychiatry, Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA 19104, USA.
FAU - Samson, Willis K
AU  - Samson WK
AD  - Department of Pharmacology and Physiology, Saint Louis University School of 
      Medicine, 1402 S. Grand Boulevard, Saint Louis, MO 63104, USA.
FAU - Yosten, Gina L C
AU  - Yosten GLC
AD  - Department of Pharmacology and Physiology, Saint Louis University School of 
      Medicine, 1402 S. Grand Boulevard, Saint Louis, MO 63104, USA.
FAU - Stein, Lauren
AU  - Stein L
AD  - Department of Psychiatry, Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA 19104, USA.
FAU - Hayes, Matthew R
AU  - Hayes MR
AUID- ORCID: 0000-0001-9782-6551
AD  - Department of Psychiatry, Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA 19104, USA.
LA  - eng
GR  - DK118340/DK/NIDDK NIH HHS/United States
GR  - DK115762/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20230511
PL  - Switzerland
TA  - Nutrients
JT  - Nutrients
JID - 101521595
SB  - IM
MH  - Rats
MH  - Male
MH  - Animals
MH  - Rats, Sprague-Dawley
MH  - *Vagus Nerve/metabolism
MH  - *Solitary Nucleus
MH  - Neurons
PMC - PMC10221706
OTO - NOTNLM
OT  - CART
OT  - GPR-160
OT  - dorsal vagal complex
OT  - feeding
OT  - microglia
COIS- M.R.H. and B.C.R. received research funding from Novo Nordisk, Eli Lilly, Gila 
      Therapeutics, and Boehringer Ingelheim that was not used in support of these 
      studies. M.R.H. is CEO of Cantius Therapeutics, LLC that pursues biological work 
      unrelated to the current study. All other authors declare no competing interests.
EDAT- 2023/05/27 09:42
MHDA- 2023/05/29 06:42
PMCR- 2023/05/11
CRDT- 2023/05/27 01:26
PHST- 2023/04/11 00:00 [received]
PHST- 2023/04/28 00:00 [revised]
PHST- 2023/05/03 00:00 [accepted]
PHST- 2023/05/29 06:42 [medline]
PHST- 2023/05/27 09:42 [pubmed]
PHST- 2023/05/27 01:26 [entrez]
PHST- 2023/05/11 00:00 [pmc-release]
AID - nu15102268 [pii]
AID - nutrients-15-02268 [pii]
AID - 10.3390/nu15102268 [doi]
PST - epublish
SO  - Nutrients. 2023 May 11;15(10):2268. doi: 10.3390/nu15102268.