Nucleus accumbens inflammation mediates anxiodepressive behavior and compulsive sucrose seeking elicited by saturated dietary fat.
Nucleus accumbens inflammation mediates anxiodepressive behavior and compulsive sucrose seeking elicited by saturated dietary fat.
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DOI：
10.1016/j.molmet.2018.01.018
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发表时间：
2018-04
影响因子：
8.1
通讯作者：
Fulton S
中科院分区：
文献类型：
--
作者：
Décarie-Spain L;Sharma S;Hryhorczuk C;Issa-Garcia V;Barker PA;Arbour N;Alquier T;Fulton S
抑郁症的发病率与肥胖症密切相关。由过量摄入高脂肪食物引起的肥胖引起焦虑抑郁行为和兴奋性神经核（NAc）中的分子适应，该区域与抑郁相关的享乐缺陷和食物动机行为的控制密切相关。为了确定饮食诱导的抑郁症的病因，我们研究了不同饮食脂质对焦虑抑郁行为、代谢和免疫结果的影响以及NAc免疫活性的贡献。成年C57 Bl/6小鼠接受富含饱和或单不饱和脂肪的等热量高脂肪/高蔗糖饮食（HFD）或对照低脂饮食（LFD）。12周后评估代谢反应、焦虑抑郁行为、血浆和NAc炎症标志物。在单独的实验中，将抑制IKKβ（核因子κ B（NFkB）途径的上游组分）的腺病毒构建体事先注射到NAc中。两种HFD均导致肥胖和高瘦素血症;然而，饱和HFD独特地触发焦虑样行为、行为绝望、高胰岛素血症、葡萄糖耐受不良、外周炎症和NAc中的多种促炎性体征，包括反应性神经胶质增生、细胞因子、抗原呈递标记物和NF κ B转录活性表达增加。选择性NAc IKKβ抑制逆转了炎症标志物的上调表达，防止了喂食饱和HFD的小鼠的焦虑抑郁行为，并减弱了强迫性蔗糖寻求。NAc中的代谢性炎症和NFк B介导的神经炎症反应有助于表达焦虑抑郁行为和由高饱和脂肪和糖饮食引起的食物渴望。饱和HFD独特地触发代谢障碍和抑郁行为。脑桥核（NAc）炎症和神经胶质增生是饱和HFD的独特特征。IKKβ/NFκB信号通路介导抑郁行为和NAc免疫激活。抑制NAc IKKβ/NFκB可抑制喂食饱和HFD的小鼠的强迫性蔗糖寻求。
The incidence of depression is significantly compounded by obesity. Obesity arising from excessive intake of high-fat food provokes anxiodepressive behavior and elicits molecular adaptations in the nucleus accumbens (NAc), a region well-implicated in the hedonic deficits associated with depression and in the control of food-motivated behavior. To determine the etiology of diet-induced depression, we studied the impact of different dietary lipids on anxiodepressive behavior and metabolic and immune outcomes and the contribution of NAc immune activity. Adult C57Bl/6 mice were subjected to isocaloric high-fat/high-sucrose diets (HFD), enriched in either saturated or monounsaturated fat, or a control low-fat diet (LFD). Metabolic responses, anxiodepressive behavior, and plasma and NAc inflammatory markers were assessed after 12 weeks. In separate experiments, an adenoviral construct inhibiting IKKβ, an upstream component of the nuclear factor kappa-b (NFkB) pathway, was a priori injected into the NAc. Both HFDs resulted in obesity and hyperleptinemia; however, the saturated HFD uniquely triggered anxiety-like behavior, behavioral despair, hyperinsulinemia, glucose intolerance, peripheral inflammation, and multiple pro-inflammatory signs in the NAc, including reactive gliosis, increased expression of cytokines, antigen-presenting markers and NFкB transcriptional activity. Selective NAc IKKβ inhibition reversed the upregulated expression of inflammatory markers, prevented anxiodepressive behavior and blunted compulsive sucrose-seeking in mice fed the saturated HFD. Metabolic inflammation and NFкB-mediated neuroinflammatory responses in the NAc contribute to the expression of anxiodepressive behavior and heightened food cravings caused by a diet high in saturated fat and sugar. Saturated HFD uniquely triggers metabolic impairments & depressive behavior. Nucleus accumbens (NAc) inflammation & gliosis are distinct features of the saturated HFD. Depressive behavior & NAc immune activation are mediated by IKKβ/NFκB signaling. Inhibiting NAc IKKβ/NFκB suppresses compulsive sucrose seeking in mice fed the saturated HFD.
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影响因子：
3.7
作者：
Chirinos DA;Murdock KW;LeRoy AS;Fagundes C
通讯作者：
Fagundes C
影响因子：
11
作者：
Hamer, M.;Batty, G. D.;Kivimaki, M.
通讯作者：
Kivimaki, M.
影响因子：
11
作者：
Aguliar-Valles, A.;Kim, J.;Luheshi, G. N.
通讯作者：
Luheshi, G. N.
影响因子：
29
作者：
Fernandes, Maria Fernanda A.;Matthys, Dominique;Fulton, Stephanie
通讯作者：
Fulton, Stephanie
影响因子：
10.6
作者：
Dowlati, Yekta;Herrmann, Nathan;Lanctot, Krista L.
通讯作者：
Lanctot, Krista L.