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高脂肪摄入和肥胖相关参数可预测 cafeteria 饮食喂养大鼠纹状体脑源性神经营养因子基因表达和多巴胺代谢物水平。

Fat Intake and Obesity-related Parameters Predict Striatal BDNF Gene Expression and Dopamine Metabolite Levels in Cafeteria Diet-fed Rats.

机构信息

Instituto de Investigaciones en Salud, Universidad de Costa Rica, San José, Costa Rica.

Laboratorio de Ensayos Biológicos, Universidad de Costa Rica, San José, Costa Rica.

出版信息

Neuroscience. 2022 May 21;491:225-239. doi: 10.1016/j.neuroscience.2022.03.042. Epub 2022 Apr 6.

DOI:10.1016/j.neuroscience.2022.03.042
PMID:35398176
Abstract

Modern westernized diet is a major risk factor associated with the current obesity epidemic. To study the effects of dietary choices of Western societies, the cafeteria diet has been validated as a preclinical model of obesity. We aimed to investigate the behavioral and metabolic alterations induced by a cafeteria diet on gene expression and neurotransmitter contents involved in neural plasticity and reward processing. Male Wistar rats were exposed to either standard or cafeteria diet for 9 weeks. Food intake and body weight were scored daily. Behavioral effects were assessed in the elevated plus-maze (EPM) and open field (OFT) tests. Serum biochemical parameters, brain monoamines, and BDNF, TrkB, CRF, CREB, and Dnmt3A mRNA levels were analyzed in reward-related brain regions. We found that cafeteria-diet rats consumed more energy and food than the control group, leading to increased body weight gain and adiposity. The cafeteria-diet rats showed an anxiolytic-like effect in the OFT, but not in the EPM. The cafeteria diet increased BDNF expression in the dorsal striatum (DS), and norepinephrine, 5-HT, TrkB, CREB, and Dnmt3A levels in the hippocampus. Additionally, multiple regression analysis showed that accumbal DOPAC and BDNF mRNA levels were robustly predicted by hyperphagia, fat mass accumulation, and body weight gain only in the cafeteria group. Overall, cafeteria diet-induced hyperphagia could lead to alterations in hedonic and motivational control of food intake through changes in dopamine metabolism and BDNF signaling in the nucleus accumbens and the DS.

摘要

现代西式饮食是当前肥胖流行的一个主要危险因素。为了研究西方社会饮食选择的影响, cafeteria 饮食已被验证为肥胖的临床前模型。我们旨在研究 cafeteria 饮食对涉及神经可塑性和奖励处理的基因表达和神经递质含量的行为和代谢改变。雄性 Wistar 大鼠暴露于标准或 cafeteria 饮食 9 周。每天记录食物摄入量和体重。在高架十字迷宫(EPM)和旷场(OFT)测试中评估行为效应。分析与奖励相关的大脑区域中的血清生化参数、脑单胺、BDNF、TrkB、CRF、CREB 和 Dnmt3A mRNA 水平。我们发现 cafeteria 饮食组大鼠比对照组大鼠消耗更多的能量和食物,导致体重增加和肥胖。 cafeteria 饮食组大鼠在 OFT 中表现出类似焦虑的效果,但在 EPM 中没有。 cafeteria 饮食增加了背侧纹状体(DS)中的 BDNF 表达,以及海马中的去甲肾上腺素、5-HT、TrkB、CREB 和 Dnmt3A 水平。此外,多元回归分析表明,仅在 cafeteria 组中,伏隔核的 DOPAC 和 BDNF mRNA 水平与多食、脂肪质量积累和体重增加呈强相关。总的来说, cafeteria 饮食诱导的多食可能通过伏隔核和 DS 中多巴胺代谢和 BDNF 信号的变化,导致对食物摄入的享乐和动机控制的改变。

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