Objective

Orexin (ORX) and melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus are critical regulators of energy homeostasis and are thought to differentially contribute to diet-induced obesity. However, it is unclear whether the synaptic properties of these cells are altered by obesogenic diets over time.

Methods

Rats and mice were fed a control chow or palatable high-fat diet (HFD) for various durations and then synaptic properties of ORX and MCH neurons were examined using ex vivo whole-cell patch clamp recording. Confocal imaging was performed to assess the number of excitatory synaptic contacts to these neurons.

Results

ORX neurons exhibited a transient increase in spontaneous excitatory transmission as early as 1 day up to 1 week of HFD, which returned to control levels with prolonged feeding. Conversely, HFD induced a delayed increase in excitatory synaptic transmission to MCH neurons, which progressively increased as HFD became chronic. This increase occurred before the onset of significant weight gain. These synaptic changes appeared to be due to altered postsynaptic sensitivity or the number of active synaptic contacts depending on cell type and feeding duration. However, HFD induced no change in inhibitory transmission in either cell type at any time point.

Conclusions

These results suggest that the effects of HFD on feeding-related neurons are cell type-specific and dynamic. This highlights the importance of considering the feeding duration for research and weight loss interventions. ORX neurons may contribute to early hyperphagia, whereas MCH neurons may play a role in the onset and long-term maintenance of diet-induced obesity.

中文翻译：

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高脂饮食诱导下丘脑外侧的时间依赖性突触可塑性。

目的

下丘脑外侧的Orexin（ORX）和黑色素浓缩激素（MCH）神经元是能量稳态的关键调节器，被认为对饮食诱导的肥胖有不同的贡献。然而，尚不清楚这些成脂饮食是否会随着时间的推移而改变这些细胞的突触特性。

方法

给大鼠和小鼠喂食对照食物或可口的高脂饮食（HFD）不同的时间，然后使用离 体全细胞膜片钳记录检查ORX和MCH神经元的突触特性。进行共聚焦成像以评估与这些神经元的兴奋性突触接触的数量。

结果

早在HFD的1周至1周，ORX神经元就表现出自发性兴奋性传递的短暂增加，随着进食时间的延长，其恢复到控制水平。相反，HFD导致向MCH神经元的兴奋性突触传递延迟增加，并随着HFD变得慢性而逐渐增加。这种增加发生在体重明显增加之前。这些突触的变化似乎是由于突触后敏感性的改变或有效的突触接触数量的变化所致，具体取决于细胞类型和进食时间。但是，HFD在任何时间点都不会引起任何一种细胞类型的抑制性传递变化。

结论

这些结果表明，HFD对进食相关神经元的影响是细胞类型特异性的和动态的。这突出了考虑研究和减肥干预措施的喂养时间的重要性。ORX神经元可能导致早期食欲亢进，而MCH神经元可能在饮食引起的肥胖的发作和长期维持中发挥作用。