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Short-term high-fat feeding induces a reversible net decrease in synaptic AMPA receptors in the hypothalamus
The Journal of Nutritional Biochemistry ( IF 5.6 ) Pub Date : 2020-10-03 , DOI: 10.1016/j.jnutbio.2020.108516
Jianfeng Liu 1 , Stoyan Dimitrov 2 , Anuck Sawangjit 1 , Jan Born 2 , Ingrid Ehrlich 3 , Manfred Hallschmid 2
Affiliation  

Dietary obesity compromises brain function, but the effects of high-fat food on synaptic transmission in hypothalamic networks, as well as their potential reversibility, are yet to be fully characterized. We investigated the impact of high-fat feeding on a hallmark of synaptic plasticity, i.e., the expression of glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) that contain the subunits GluA1 and GluA2, in hypothalamic and cortical synaptoneurosomes of male rats. In the main experiment (experiment 1), three days, but not one day of high-fat diet (HFD) decreased the levels of AMPAR GluA1 and GluA2 subunits, as well as GluA1 phosphorylation at Ser845, in hypothalamus but not cortex. In experiment 2, we compared the effects of the three-day HFD with those a three-day HFD followed by four recovery days of normal chow. This experiment corroborated the suppressive effect of high-fat feeding on hypothalamic but not cortical AMPAR GluA1, GluA2, and GluA1 phosphorylation at Ser845, and indicated that the effects are reversed by normal-chow feeding. High-fat feeding generally increased energy intake, body weight, and serum concentrations of insulin, leptin, free fatty acids, and corticosterone; only the three-day HFD increased wakefulness assessed via video analysis. Results indicate a reversible down-regulation of hypothalamic glutamatergic synaptic strength in response to short-term high-fat feeding. Preceding the manifestation of obesity, this rapid change in glutamatergic neurotransmission may underlie counter-regulatory efforts to prevent excess body weight gain, and therefore, represent a new target of interventions to improve metabolic control.



中文翻译:

短期高脂肪喂养诱导下丘脑突触AMPA受体的可逆净减少

饮食肥胖会损害大脑功能,但高脂肪食物对下丘脑网络突触传递的影响及其潜在的可逆性尚未得到充分表征。我们研究了高脂肪喂养对突触可塑性标志的影响,,包含亚基 GluA1 和 GluA2 的谷氨酸能 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体 (AMPAR) 在雄性大鼠的下丘脑和皮质突触神经体中的表达。在主要实验(实验 1)中,三天而非一天的高脂肪饮食 (HFD) 降低了下丘脑而非皮质中 AMPAR GluA1 和 GluA2 亚基的水平,以及 Ser845 处的 GluA1 磷酸化水平。在实验 2 中,我们比较了三天 HFD 与三天 HFD 和四个恢复天正常食物的效果。该实验证实了高脂肪喂养对下丘脑而非皮质 AMPAR GluA1、GluA2 和 GluA1 Ser845 磷酸化的抑制作用,并表明正常饲料喂养可逆转这种影响。高脂喂养一般会增加能量摄入,体重、胰岛素、瘦素、游离脂肪酸和皮质酮的血清浓度;只有三天的 HFD 增加了通过视频分析评估的清醒度。结果表明响应短期高脂肪喂养的下丘脑谷氨酸能突触强度可逆下调。在肥胖表现之前,谷氨酸能神经传递的这种快速变化可能是防止体重过度增加的反调节努力的基础,因此代表了改善代谢控制的干预措施的新目标。

更新日期:2020-10-30
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