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MC4R Deficiency Causes Dysregulation of Postsynaptic Excitatory Synaptic Transmission as a Crucial Culprit for Obesity.

Authors :
Wang, Xiaohui
Cui, Xiaoli
Li, Yang
Li, Fei
Li, Yue
Dai, Jinye
Hu, Han
Wang, Xuefeng
Sun, Jianyuan
Yang, Yan
Zhang, Shuli
Source :
Diabetes; Nov2022, Vol. 71 Issue 11, p2331-2343, 13p
Publication Year :
2022

Abstract

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00121797
Volume :
71
Issue :
11
Database :
Complementary Index
Journal :
Diabetes
Publication Type :
Academic Journal
Accession number :
160660807
Full Text :
https://doi.org/10.2337/db22-0162