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饱和而非单不饱和膳食脂质对中脑边缘多巴胺功能及信号传导的抑制作用

Dampened Mesolimbic Dopamine Function and Signaling by Saturated but not Monounsaturated Dietary Lipids.

作者信息

Hryhorczuk Cecile, Florea Marc, Rodaros Demetra, Poirier Isabelle, Daneault Caroline, Des Rosiers Christine, Arvanitogiannis Andreas, Alquier Thierry, Fulton Stephanie

机构信息

Centre de Recherche du CHUM and Montreal Diabetes Research Center, Montreal, QC, Canada.

Department of Physiology, Université de Montréal, Montreal, QC, Canada.

出版信息

Neuropsychopharmacology. 2016 Feb;41(3):811-21. doi: 10.1038/npp.2015.207. Epub 2015 Jul 14.

Abstract

Overconsumption of dietary fat is increasingly linked with motivational and emotional impairments. Human and animal studies demonstrate associations between obesity and blunted reward function at the behavioral and neural level, but it is unclear to what degree such changes are a consequence of an obese state and whether they are contingent on dietary lipid class. We sought to determine the impact of prolonged ad libitum intake of diets rich in saturated or monounsaturated fat, separate from metabolic signals associated with increased adiposity, on dopamine (DA)-dependent behaviors and to identify pertinent signaling changes in the nucleus accumbens (NAc). Male rats fed a saturated (palm oil), but not an isocaloric monounsaturated (olive oil), high-fat diet exhibited decreased sensitivity to the rewarding (place preference) and locomotor-sensitizing effects of amphetamine as compared with low-fat diet controls. Blunted amphetamine action by saturated high-fat feeding was entirely independent of caloric intake, weight gain, and plasma levels of leptin, insulin, and glucose and was accompanied by biochemical and behavioral evidence of reduced D1R signaling in the NAc. Saturated high-fat feeding was also tied to protein markers of increased AMPA receptor-mediated plasticity and decreased DA transporter expression in the NAc but not to alterations in DA turnover and biosynthesis. Collectively, the results suggest that intake of saturated lipids can suppress DA signaling apart from increases in body weight and adiposity-related signals known to affect mesolimbic DA function, in part by diminishing D1 receptor signaling, and that equivalent intake of monounsaturated dietary fat protects against such changes.

摘要

膳食脂肪摄入过多与动机和情感障碍的关联日益增加。人类和动物研究表明,肥胖与行为和神经层面的奖赏功能迟钝之间存在关联,但尚不清楚这种变化在多大程度上是肥胖状态的结果,以及它们是否取决于膳食脂质类别。我们试图确定长期随意摄入富含饱和脂肪或单不饱和脂肪的饮食(与肥胖相关的代谢信号分开)对多巴胺(DA)依赖性行为的影响,并确定伏隔核(NAc)中相关的信号变化。与低脂饮食对照组相比,喂食饱和(棕榈油)而非等热量单不饱和(橄榄油)高脂肪饮食的雄性大鼠对苯丙胺的奖赏(位置偏爱)和运动致敏作用的敏感性降低。饱和高脂肪喂养导致的苯丙胺作用迟钝完全独立于热量摄入、体重增加以及瘦素、胰岛素和葡萄糖的血浆水平,并且伴有NAc中D1R信号传导减少的生化和行为证据。饱和高脂肪喂养还与NAc中AMPA受体介导的可塑性增加和DA转运体表达降低的蛋白质标志物有关,但与DA周转和生物合成的改变无关。总体而言,结果表明,饱和脂质的摄入可以在不增加已知影响中脑边缘DA功能的体重和肥胖相关信号的情况下抑制DA信号传导,部分原因是通过减少D1受体信号传导,并且等量摄入单不饱和膳食脂肪可防止此类变化。

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