产矿性
内分泌学
内科学
奥氮平
神经肽Y受体
生长素
化学
下丘脑
黑素皮质激素受体
兴奋剂
受体
心理学
医学
神经肽
精神分裂症(面向对象编程)
精神科
作者
Xiaoli Liu,Lan Xia,Xinyou Zhang,Huaiyu Ye,Li-Jun Shen,Minmin Hu,Xiaoqi Chen,Mingxuan Zheng,Katrina Weston–Green,Tiantian Jin,Xiaoying Cui,Yi Zhou,Xiangyu Lu,Xu‐Feng Huang,Yinghua Yu
标识
DOI:10.1016/j.bbr.2024.114885
摘要
The main cause of second-generation antipsychotic (SGA)-induced obesity is considered due to the antagonism of serotonin 2c receptors (5-HT2cR) and activation of ghrelin receptor type 1a (GHSR1a) signalling. It is reported that 5-HT2cR interacted with GHSR1a, however it is unknown whether one of the SGA olanzapine alters the 5-HT2cR/GHSR1a interaction, affecting orexigenic neuropeptide signalling in the hypothalamus. We found that olanzapine treatment increased average energy intake and body weight gain in mice; olanzapine treatment also increased orexigenic neuropeptide (NPY) and GHSR1a signaling molecules, pAMPK, UCP2, FOXO1 and pCREB levels in the hypothalamus. By using confocal fluorescence resonance energy transfer (FRET) technology, we found that 5-HT2cR interacted/dimerised with the GHSR1a in the hypothalamic neurons. As 5-HT2cR antagonist, both olanzapine and S242084 decreased the interaction between 5-HT2cR and GHSR1a and activated GHSR1a signaling. The 5-HT2cR agonist lorcaserin counteracted olanzapine-induced attenuation of interaction between 5-HT2cR and GHSR1a and inhibited activation of GHSR1a signalling and NPY production. These findings suggest that 5-HT2cR antagonistic effect of olanzapine in inhibition of the interaction of 5-HT2cR and GHSR1a, activation GHSR1a downstream signaling and increasing hypothalamic NPY, which may be the important neuronal molecular mechanism underlying olanzapine-induced obesity and target for prevention metabolic side effects of antipsychotic management in psychiatric disorders.
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