Circulating Triglycerides Gate Dopamine-Associated Behaviors through DRD2-Expressing Neurons

Berland Chloe; Montalban Enrica; Perrin Elodie; Di Miceli Mathieu; Nakamura Yuko; Martinat Maud; Sullivan Mary; Davis Xue S.; Shenasa Mohammad Ali; Martin Claire; Tolu Stefania; Marti Fabio; Caille Stephanie; Castel Julien; Perez Sylvie; Salinas Casper Gravesen; Morel Chloe; Hecksher-Sorensen Jacob; Cador Martine; Fioramonti Xavier; Tschoep Matthias H.; Laye Sophie; Venance Laurent; Faure Philippe; Hnasko Thomas S.; Small Dana M.; Gangarossa Giuseppe; Luquet Serge H.

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Circulating Triglycerides Gate Dopamine-Associated Behaviors through DRD2-Expressing Neurons

机译：通过DRD2的神经元循环甘油三酯栅极多巴胺相关行为

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Energy-dense food alters dopaminergic (DA) transmission in the mesocorticolimbic (MCL) system and can promote reward dysfunctions, compulsive feeding, and weight gain. Yet the mechanisms by which nutrients influence the MCL circuitry remain elusive. Here, we show that nutritional triglycerides (TGs), a conserved post-prandial metabolic signature among mammals, can be metabolized within the MCL system and modulate DA-associated behaviors by gating the activity of dopamine receptor subtype 2 (DRD2)-expressing neurons through a mechanism that involves the action of the lipoprotein lipase (LPL). Further, we show that in humans, postprandial TG excursions modulate brain responses to food cues in individuals carrying a genetic risk for reduced DRD2 signaling. Collectively, these findings unveil a novel mechanism by which dietary TGs directly alter signaling in the reward circuit to regulate behavior, thereby providing a new mechanistic basis by which energy-rich diets may lead to (mal)adaptations in DA signaling that underlie reward deficit and compulsive behavior.

机译：能量密集的食物改变了Mesocorticolimbic（MCL）系统中的多巴胺能（DA）透射，可以促进奖励功能障碍，强迫喂养和体重增加。然而，营养影响MCL电路的机制仍然难以捉摸。在这里，我们表明营养甘油三酯（TGS）是哺乳动物中的保守后伪造代谢特征，可以通过在MCL系统内代谢，并通过促进多巴胺受体亚型2（DRD2） - 表达神经元的活性来调节DA相关行为涉及脂蛋白脂肪酶（LPL）的作用的机制。此外，我们展示了在人类中，餐后TG偏移调节对携带遗传风险的个体对DRD2信号传导的遗传风险的食物提示的大脑响应。总的来说，这些发现揭示了一种新的机制，通过该机制，膳食TGS直接改变奖励电路中的信号传导来调节行为，从而提供了一种新的机制基础，通过富能量的饮食可能导致（MAL）适应在DA信令中，奖励赤字和强迫行为。

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《Cell metabolism》 |2020年第4期|共29页
作者
Berland Chloe; Montalban Enrica; Perrin Elodie; Di Miceli Mathieu; Nakamura Yuko; Martinat Maud; Sullivan Mary; Davis Xue S.; Shenasa Mohammad Ali; Martin Claire; Tolu Stefania; Marti Fabio; Caille Stephanie; Castel Julien; Perez Sylvie; Salinas Casper Gravesen; Morel Chloe; Hecksher-Sorensen Jacob; Cador Martine; Fioramonti Xavier; Tschoep Matthias H.; Laye Sophie; Venance Laurent; Faure Philippe; Hnasko Thomas S.; Small Dana M.; Gangarossa Giuseppe; Luquet Serge H.;
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Univ Paris CNRS BFA UMR 8251 F-75014 Paris France;

Univ Paris CNRS BFA UMR 8251 F-75014 Paris France;

Ctr Interdisciplinary Res Biol Coll France Labex Memolife INSERM U1050 CNRS UMR 7241 F-75005;

Univ Bordeaux NutriNeuro Bordeaux INP INRA UMR 1286 F-33000 Bordeaux France;

Modern Diet &

Physiol Res Ctr New Haven CT 06510 USA;

Univ Bordeaux NutriNeuro Bordeaux INP INRA UMR 1286 F-33000 Bordeaux France;

Modern Diet &

Physiol Res Ctr New Haven CT 06510 USA;

Modern Diet &

Physiol Res Ctr New Haven CT 06510 USA;

Univ Calif San Diego Dept Neurosci La Jolla CA 92093 USA;

Univ Paris CNRS BFA UMR 8251 F-75014 Paris France;

Sorbonne Univ Inst Biol Paris Seine Neurosci Paris Seine INSERM CNRS UMR 8246 Paris France;

Sorbonne Univ Inst Biol Paris Seine Neurosci Paris Seine INSERM CNRS UMR 8246 Paris France;

Univ Bordeaux Inst Neurosci Cognit &

Integrat Aquitaine UMR5287 CNRS F-33076 Bordeaux France;

Univ Paris CNRS BFA UMR 8251 F-75014 Paris France;

Ctr Interdisciplinary Res Biol Coll France Labex Memolife INSERM U1050 CNRS UMR 7241 F-75005;

Gubra ApS Hrsholm Kongevej 11B DK-2970 Horsholm Denmark;

Univ Paris CNRS BFA UMR 8251 F-75014 Paris France;

Novo Nordisk AS Global Res Malov Denmark;

Univ Bordeaux Inst Neurosci Cognit &

Integrat Aquitaine UMR5287 CNRS F-33076 Bordeaux France;

Univ Bordeaux NutriNeuro Bordeaux INP INRA UMR 1286 F-33000 Bordeaux France;

Helmholtz Zentrum Munchen German Res Ctr Environm Hlth Helmholtz Diabet Ctr Neuherberg Germany;

Univ Bordeaux NutriNeuro Bordeaux INP INRA UMR 1286 F-33000 Bordeaux France;

Ctr Interdisciplinary Res Biol Coll France Labex Memolife INSERM U1050 CNRS UMR 7241 F-75005;

Sorbonne Univ Inst Biol Paris Seine Neurosci Paris Seine INSERM CNRS UMR 8246 Paris France;

Univ Calif San Diego Dept Neurosci La Jolla CA 92093 USA;

Modern Diet &

Physiol Res Ctr New Haven CT 06510 USA;

Univ Paris CNRS BFA UMR 8251 F-75014 Paris France;

Univ Paris CNRS BFA UMR 8251 F-75014 Paris France;

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正文语种 eng
中图分类内分泌腺疾病及代谢病;
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专利

1. Circulating Triglycerides Gate Dopamine-Associated Behaviors through DRD2-Expressing Neurons [J] . Berland Chloe, Montalban Enrica, Perrin Elodie, Cell metabolism . 2020,第4期

机译：通过DRD2的神经元循环甘油三酯栅极多巴胺相关行为
2. Light-regulated voltage-gated potassium channels for acute interrogation of channel function in neurons and behavior [J] . Henry H. Jerng, Jay M. Patel, Tamor A. Khan, PLoS One . 2021,第3期

机译：用于急性询问神经元和行为中的急性询问的光调节电压门控钾通道
3. Short Communication: An Updated Design to Implement Artificial Neuron Synaptic Behaviors in One Device with a Control Gate [J] . Shaocheng Qi, Yongbin Hu, Chaoqi Dai, International Journal of Nanomedicine . 2020,第1期

机译：短期通信：更新的设计，用于使用控制门的一个设备中的人工神经元突触行为实施
4. Low-density lipoprotein, triglycerides and glycated haemoglobin as metabolic determinant factors of superoxide dismutase circulating levels. [C] . Alonso A., Fabregate M., Fabregate R., International Congress on Coronary Artery Disease . 2009

机译：低密度脂蛋白，甘油三酯和糖化血红蛋白作为超氧化物歧化酶循环水平的代谢决定因子。
5. G Protein-Gated Potassium Channels in Ventral Tegmental Area Dopamine Neurons Temper Behavioral Sensitivity to Cocaine [D] . McCall, Nora Marie. 2019

机译：G型腹膜型钾通道在腹侧腹部区域多巴胺神经元脾气暴行对可卡因的敏感性
6. Inhibitory Effects of Columbianadin on Nociceptive Behaviors in a Neuropathic Pain Model and on Voltage-Gated Calcium Currents in Dorsal Root Ganglion Neurons in Mice [O] . Xiaolin Su, Bin Wu, Wentong Zhang, 2019

机译：哥伦比亚多蛋白对神经病疼痛模型中伤害性行为的抑制作用小鼠背根神经节神经元的电压门控钙电流
7. Inhibitory Effects of Columbianadin on Nociceptive Behaviors in a Neuropathic Pain Model, and on Voltage-Gated Calcium Currents in Dorsal Root Ganglion Neurons in Mice [O] . Xiaolin Su, Bin Wu, Wentong Zhang, 2020

机译：哥伦比亚多蛋白对神经病疼痛模型中伤害性行为的抑制作用，小鼠背根神经节神经元的电压门控钙电流

Circulating Triglycerides Gate Dopamine-Associated Behaviors through DRD2-Expressing Neurons

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