PMID- 35926095
OWN - NLM
STAT- MEDLINE
DCOM- 20221025
LR  - 20221220
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Linking)
VI  - 71
IP  - 11
DP  - 2022 Nov 1
TI  - MC4R Deficiency Causes Dysregulation of Postsynaptic Excitatory Synaptic 
      Transmission as a Crucial Culprit for Obesity.
PG  - 2331-2343
LID - 10.2337/db22-0162 [doi]
AB  - Melanocortin 4 receptor (MC4R) in the paraventricular nucleus of the hypothalamus 
      (PVH) shows bidirectional characterization in modulating food intake and energy 
      homeostasis. We demonstrate that MC4R knockdown (KD) in the PVH can attenuate 
      AMPA receptor (AMPAR)-mediated postsynaptic responses by altering the 
      phosphorylation of AMPAR GluA1 subunit through the protein kinase A 
      (PKA)-dependent signaling cascade and simultaneously lead to rapid body weight 
      gain. Furthermore, PKA KD in the PVH engendered similar electrophysiological and 
      behavioral phenotypes as in MC4R KD mice. Importantly, we observed that the 
      reduction of AMPAR GluA1 expression not only led to attenuated synaptic responses 
      but also caused body weight gain, suggesting that the aberration of synaptic 
      responses may be one of the crucial pathogeny of obesity. Our study provides the 
      synaptic and molecular explanations of how body weight is regulated by MC4R in 
      the PVH.
CI  - (c) 2022 by the American Diabetes Association.
FAU - Wang, Xiaohui
AU  - Wang X
AD  - Department of General Surgery, Xuanwu Hospital, Capital Medical University, 
      Beijing, China.
FAU - Cui, Xiaoli
AU  - Cui X
AD  - State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, 
      Chinese Academy of Sciences, Beijing, China.
AD  - Chinese Institute for Brain Research, Beijing, China.
AD  - University of Chinese Academy of Sciences, Beijing, China.
FAU - Li, Yang
AU  - Li Y
AD  - State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, 
      Chinese Academy of Sciences, Beijing, China.
AD  - University of Chinese Academy of Sciences, Beijing, China.
FAU - Li, Fei
AU  - Li F
AD  - Department of General Surgery, Xuanwu Hospital, Capital Medical University, 
      Beijing, China.
FAU - Li, Yue
AU  - Li Y
AD  - Guangwai Community Health Service Center of Xicheng District, Beijing, China.
FAU - Dai, Jinye
AU  - Dai J
AD  - Howard Hughes Medical Institute and Department of Molecular and Cellular 
      Physiology, Stanford University, Stanford, CA.
FAU - Hu, Han
AU  - Hu H
AD  - State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, 
      Chinese Academy of Sciences, Beijing, China.
AD  - University of Chinese Academy of Sciences, Beijing, China.
FAU - Wang, Xuefeng
AU  - Wang X
AD  - State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, 
      Chinese Academy of Sciences, Beijing, China.
AD  - University of Chinese Academy of Sciences, Beijing, China.
FAU - Sun, Jianyuan
AU  - Sun J
AD  - State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, 
      Chinese Academy of Sciences, Beijing, China.
AD  - University of Chinese Academy of Sciences, Beijing, China.
AD  - The Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced 
      Technology, Chinese Academy of Sciences, Beijing, China.
FAU - Yang, Yan
AU  - Yang Y
AD  - State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, 
      Chinese Academy of Sciences, Beijing, China.
AD  - University of Chinese Academy of Sciences, Beijing, China.
FAU - Zhang, Shuli
AU  - Zhang S
AUID- ORCID: 0000-0001-8006-1134
AD  - State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, 
      Chinese Academy of Sciences, Beijing, China.
AD  - University of Chinese Academy of Sciences, Beijing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - 0 (MC4R protein, mouse)
RN  - 0 (Receptor, Melanocortin, Type 4)
RN  - 0 (Receptors, AMPA)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Body Weight
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - *Obesity/metabolism
MH  - *Receptor, Melanocortin, Type 4/genetics/metabolism
MH  - Receptors, AMPA/genetics/metabolism
MH  - Synaptic Transmission
EDAT- 2022/08/05 06:00
MHDA- 2022/10/25 06:00
CRDT- 2022/08/04 14:42
PHST- 2022/02/16 00:00 [received]
PHST- 2022/07/30 00:00 [accepted]
PHST- 2022/08/05 06:00 [pubmed]
PHST- 2022/10/25 06:00 [medline]
PHST- 2022/08/04 14:42 [entrez]
AID - 147382 [pii]
AID - 10.2337/db22-0162 [doi]
PST - ppublish
SO  - Diabetes. 2022 Nov 1;71(11):2331-2343. doi: 10.2337/db22-0162.