Dopamine production in neurotensin receptor 1 neurons is required for diet-induced obesity and increased day eating on a high-fat diet

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Obesity Pub Date : 2024-07-09 DOI:10.1002/oby.24066
Firozeh Farahmand, Michael Sidikpramana, Alyssa R. Gomez, Luis J. Rivera, Jacqueline R. Trzeciak, Sarah Sharif, Qijun Tang, Gina M. Leinninger, Ali D. Güler, Andrew D. Steele
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Abstract

Objective

This study aimed to determine a dopaminergic circuit required for diet-induced obesity in mice.

Methods

We created conditional deletion mutants for tyrosine hydroxylase (TH) using neurotensin receptor 1 (Ntsr1) Cre and other Cre drivers and measured feeding and body weight on standard and high-fat diets. We then used an adeno-associated virus to selectively restore TH to the ventral tegmental area (VTA) Ntsr1 neurons in conditional knockout (cKO) mice.

Results

Mice with cKO of Th using Vglut2-Cre, Cck-Cre, Calb1-Cre, and Bdnf-Cre were susceptible to obesity on a high-fat diet; however, Ntsr1-Cre Th cKO mice resisted weight gain on a high-fat diet and did not experience an increase in day eating unlike their wild-type littermate controls. Restoration of TH to the VTA Ntsr1 neurons of the Ntsr1-Cre Th cKO mice using an adeno-associated virus resulted in an increase in weight gain and day eating on a high-fat diet.

Conclusions

Ntsr1-Cre Th cKO mice failed to increase day eating on a high-fat diet, offering a possible explanation for their resistance to diet-induced obesity. These results implicate VTA Ntsr1 dopamine neurons as promoting out-of-phase feeding behavior on a high-fat diet that could be an important contributor to diet-induced obesity in humans.

Abstract Image

多巴胺在神经紧张素受体1神经元中的分泌是饮食诱发肥胖和高脂饮食日进食量增加所必需的。
目的:本研究旨在确定饮食诱导小鼠肥胖所需的多巴胺能回路:本研究旨在确定饮食诱导小鼠肥胖所需的多巴胺能回路:我们利用神经紧张素受体 1(Ntsr1)Cre 和其他 Cre 驱动因子创建了酪氨酸羟化酶(TH)的条件性缺失突变体,并测量了小鼠在标准和高脂饮食下的摄食量和体重。然后,我们使用腺相关病毒在条件性基因敲除(cKO)小鼠的腹侧被盖区(VTA)Ntsr1神经元中选择性地恢复TH:结果:使用Vglut2-Cre、Cck-Cre、Calb1-Cre和Bdnf-Cre对TH进行cKO的小鼠在高脂饮食中易患肥胖症;然而,Ntsr1-Cre Th cKO小鼠在高脂饮食中体重不会增加,而且与野生型同窝对照组不同,日进食量不会增加。使用腺相关病毒恢复Ntsr1-Cre Th cKO小鼠VTA Ntsr1神经元的TH,结果是在高脂饮食中体重增加和日进食量增加:结论:Ntsr1-Cre Th cKO小鼠在高脂饮食中不能增加日进食量,这为它们抵抗饮食诱导的肥胖提供了可能的解释。这些结果表明,VTA Ntsr1多巴胺神经元促进了高脂饮食中的失调摄食行为,这可能是饮食诱发人类肥胖症的一个重要原因。
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来源期刊
Obesity
Obesity 医学-内分泌学与代谢
CiteScore
11.70
自引率
1.40%
发文量
261
审稿时长
2-4 weeks
期刊介绍: Obesity is the official journal of The Obesity Society and is the premier source of information for increasing knowledge, fostering translational research from basic to population science, and promoting better treatment for people with obesity. Obesity publishes important peer-reviewed research and cutting-edge reviews, commentaries, and public health and medical developments.
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