Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14875-80. doi: 10.1073/pnas.1004282107. Epub 2010 Aug 2.
The neuronal circuits involved in the regulation of feeding behavior and energy expenditure are soft-wired, reflecting the relative activity of the postsynaptic neuronal system, including the anorexigenic proopiomelanocortin (POMC)-expressing cells of the arcuate nucleus. We analyzed the synaptic input organization of the melanocortin system in lean rats that were vulnerable (DIO) or resistant (DR) to diet-induced obesity. We found a distinct difference in the quantitative and qualitative synaptology of POMC cells between DIO and DR animals, with a significantly greater number of inhibitory inputs in the POMC neurons in DIO rats compared with DR rats. When exposed to a high-fat diet (HFD), the POMC cells of DIO animals lost synapses, whereas those of DR rats recruited connections. In both DIO rats and mice, the HFD-triggered loss of synapses on POMC neurons was associated with increased glial ensheathment of the POMC perikarya. The altered synaptic organization of HFD-fed animals promoted increased POMC tone and a decrease in the stimulatory connections onto the neighboring neuropeptide Y (NPY) cells. Exposure to HFD was associated with reactive gliosis, and this affected the structure of the blood-brain barrier such that the POMC and NPY cell bodies and dendrites became less accessible to blood vessels. Taken together, these data suggest that consumption of an HFD has a major impact on the cytoarchitecture of the arcuate nucleus in vulnerable subjects, with changes that might be irreversible due to reactive gliosis.
参与调节摄食行为和能量消耗的神经元回路是软连接的，反映了突触后神经元系统的相对活性，包括弓状核中表达厌食素的 proopiomelanocortin (POMC) 细胞。我们分析了易患（DIO）或抵抗（DR）饮食诱导肥胖的瘦鼠中黑素皮质素系统的突触输入组织。我们发现，DIO 和 DR 动物之间 POMC 细胞的突触组织在数量和质量上存在明显差异，DIO 大鼠的 POMC 神经元中抑制性输入明显多于 DR 大鼠。当暴露于高脂肪饮食（HFD）时，DIO 动物的 POMC 细胞失去了突触，而 DR 大鼠的 POMC 细胞则募集了连接。在 DIO 大鼠和小鼠中，HFD 触发的 POMC 神经元突触丢失与 POMC 胞体的胶质鞘形成增加有关。HFD 喂养动物改变的突触组织促进了 POMC 张力的增加，并减少了对邻近神经肽 Y (NPY) 细胞的刺激连接。暴露于 HFD 与反应性神经胶质增生有关，这会影响血脑屏障的结构，使得 POMC 和 NPY 细胞体和树突对血管的可及性降低。总之，这些数据表明，HFD 的摄入对易患个体弓状核的细胞结构有重大影响，由于反应性神经胶质增生，这些变化可能是不可逆转的。
