Dopamine D2 receptor signaling in the brain modulates circadian liver metabolomic profiles.
Dopamine D2 receptor signaling in the brain modulates circadian liver metabolomic profiles.
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DOI：
10.1073/pnas.2117113119
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发表时间：
2022-03-15
影响因子：
11.1
通讯作者：
Sassone-Corsi P
中科院分区：
文献类型：
--
作者：
Cervantes M;Lewis RG;Della-Fazia MA;Borrelli E;Sassone-Corsi P
我们分析了纹状体中棘神经元（iMSN-D2 RKO）中多巴胺D2受体（D2 R）表达缺陷的小鼠的肝脏代谢组，发现与对照小鼠相比，肝脏昼夜节律代谢组发生了深刻的变化。此外，我们显示了在iMSN-D2 RKO小鼠中通过急性可卡因给药激活多巴胺能回路，重新编程响应可卡因的昼夜肝脏代谢组。MSNs中的D2 R信号传导是纹状体输出的关键，并且对于调节对可卡因的细胞和奖励效应的第一反应至关重要。我们的研究结果表明，特定纹状体神经元中多巴胺信号的变化引起肝脏生理学的重大变化。肝脏代谢的失调可能导致改变的非稳态状态，因此与持续使用药物有关。生物钟与新陈代谢紧密相关，并在很大程度上依赖于器官系统之间的多方面相互作用来保持适当的时间。遗传和/或环境原因可能会破坏器官之间的交流，改变节律活动。物质的使用导致多巴胺信号的改变，随后是奖励系统中昼夜节律基因表达和代谢的重新编程。然而，大脑中多巴胺信号的改变是否会影响外周器官的昼夜代谢还没有得到充分的研究。我们发现，多巴胺D2受体（D2 R）在纹状体中型棘神经元（MSN）在调节昼夜肝脏代谢活动中起着关键作用。此外，增加多巴胺水平的药物，如可卡因，会破坏肝脏中的昼夜代谢特征，这会因MSN中D2 R信号的丢失而加剧。这些结果揭示了神经元/脑区和肝脏代谢之间的严格沟通，以及物质使用和全身性缺陷之间的关联。
We analyzed the liver metabolome of mice deficient in the expression of the dopamine D2 receptor (D2R) in striatal medium spiny neurons (iMSN-D2RKO) and found profound changes in the liver circadian metabolome compared to control mice. Additionally, we show activation of dopaminergic circuits by acute cocaine administration in iMSN-D2RKO mice reprograms the circadian liver metabolome in response to cocaine. D2R signaling in MSNs is key for striatal output and essential for regulating the first response to the cellular and rewarding effects of cocaine. Our results suggest changes in dopamine signaling in specific striatal neurons evoke major changes in liver physiology. Dysregulation of liver metabolism could contribute to an altered allostatic state and therefore be involved in continued use of drugs. The circadian clock is tightly intertwined with metabolism and relies heavily on multifaceted interactions between organ systems to maintain proper timing. Genetic and/or environmental causes can disrupt communication between organs and alter rhythmic activities. Substance use leads to altered dopamine signaling followed by reprogramming of circadian gene expression and metabolism in the reward system. However, whether altered dopamine signaling in the brain affects circadian metabolism in peripheral organs has not been fully explored. We show that dopamine D2 receptors (D2R) in striatal medium spiny neurons (MSNs) play a key role in regulating diurnal liver metabolic activities. In addition, drugs that increase dopamine levels, such as cocaine, disrupt circadian metabolic profiles in the liver, which is exacerbated by loss of D2R signaling in MSNs. These results uncover a strict communication between neurons/brain areas and liver metabolism as well as the association between substance use and systemic deficits.
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影响因子：
2.7
作者：
Burton AC;Nakamura K;Roesch MR
通讯作者：
Roesch MR
昼夜主义代谢的地图集揭示了时钟之间全系统的协调和通信。
影响因子：
64.5
作者：
Dyar KA;Lutter D;Artati A;Ceglia NJ;Liu Y;Armenta D;Jastroch M;Schneider S;de Mateo S;Cervantes M;Abbondante S;Tognini P;Orozco-Solis R;Kinouchi K;Wang C;Swerdloff R;Nadeef S;Masri S;Magistretti P;Orlando V;Borrelli E;Uhlenhaut NH;Baldi P;Adamski J;Tschöp MH;Eckel-Mahan K;Sassone-Corsi P
通讯作者：
Sassone-Corsi P
DOI：
10.1073/pnas.1118726109
发表时间：
2012-04-03
影响因子：
11.1
作者：
Eckel-Mahan, Kristin L.;Patel, Vishal R.;Sassone-Corsi, Paolo
通讯作者：
Sassone-Corsi, Paolo
影响因子：
25
作者：
Aizman, O;Brismar, H;Aperia, A
通讯作者：
Aperia, A
影响因子：
16
作者：
Aviram, Rona;Manella, Gal;Asher, Gad
通讯作者：
Asher, Gad