Hypothalamic 2-arachidonoylglycerol regulates multistage process of high-fat diet preferences.

Hypothalamic 2-arachidonoylglycerol regulates multistage process of high-fat diet preferences.
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DOI:
10.1371/journal.pone.0038609
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Fujiwara M
Fujiwara M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Higuchi S;Irie K;Yamaguchi R;Katsuki M;Araki M;Ohji M;Hayakawa K;Mishima S;Akitake Y;Matsuyama K;Mishima K;Mishima K;Iwasaki K;Fujiwara M

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在这项研究中,我们检查了与高脂肪饮食(HFD)偏好相关的下丘脑奖励系统的变化。我们之前报道过,在适应 HFD 的有益特性后,下丘脑 2-花生四烯酰甘油 (2-AG) 和神经胶质原纤维酸性蛋白 (GFAP) 会增加。在这里,我们假设 2-AG 增加会影响下丘脑奖励系统。条件性位置偏好测试(CPP 测试)用于评估 HFD 偏好。通过气相色谱-质谱法对下丘脑 2-AG 进行定量。通过免疫染色和蛋白质印迹检查GFAP的表达。连续 3 或 7 天食用 HFD 会增加 HFD 偏好,并短暂增加下丘脑 2-AG 水平。超过 14 天的 HFD 消费同样会增加 HFD 偏好,但会引起下丘脑 2-AG 和 GFAP 水平的持久增加。大麻素 1 受体拮抗剂 O-2050 在食用 HFD 3、7 或 14 天后降低了对 HFD 的偏好,并在食用 HFD 14 天后降低了 GFAP 的表达。食用 HFD 14 天后,星形胶质细胞代谢抑制剂氟柠檬酸盐阻断了 HFD 偏好。高水平的 2-AG 似乎会诱导 HFD 偏好,并通过大麻素系统激活下丘脑星形胶质细胞。我们认为,HFD 偏好的发展可能存在两个不同的阶段。诱导阶段涉及 2-AG 的短暂增加,而维持阶段涉及 2-AG 水平的长期持续增加和星形胶质细胞的激活。因此,下丘脑 2-AG 可能会影响 HFD 偏好的发展。
In this study, we examined alterations in the hypothalamic reward system related to high-fat diet (HFD) preferences. We previously reported that hypothalamic 2-arachidonoylglycerol (2-AG) and glial fibrillary acid protein (GFAP) were increased after conditioning to the rewarding properties of a HFD. Here, we hypothesized that increased 2-AG influences the hypothalamic reward system. The conditioned place preference test (CPP test) was used to evaluate HFD preferences. Hypothalamic 2-AG was quantified by gas chromatography-mass spectrometry. The expression of GFAP was examined by immunostaining and western blotting. Consumption of a HFD over either 3 or 7 days increased HFD preferences and transiently increased hypothalamic 2-AG levels. HFD consumption over 14 days similarly increased HFD preferences but elicited a long-lasting increase in hypothalamic 2-AG and GFAP levels. The cannabinoid 1 receptor antagonist O-2050 reduced preferences for HFDs after 3, 7, or 14 days of HFD consumption and reduced expression of GFAP after 14 days of HFD consumption. The astrocyte metabolic inhibitor Fluorocitrate blocked HFD preferences after 14 days of HFD consumption. High levels of 2-AG appear to induce HFD preferences, and activate hypothalamic astrocytes via the cannabinoid system. We propose that there may be two distinct stages in the development of HFD preferences. The induction stage involves a transient increase in 2-AG, whereas the maintenance stage involves a long lasting increase in 2-AG levels and activation of astrocytes. Accordingly, hypothalamic 2-AG may influence the development of HFD preferences.
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