Department of Experimental and Clinical Medicine, Marche Polytechnic University, Via Tronto 10/A, 60020 Ancona, Italy.
Istituto di Struttura della Materia (ISM-CNR), via del Fosso del Cavaliere 100, 00133 Roma, Italy.
Int J Mol Sci. 2021 Jul 28;22(15):8049. doi: 10.3390/ijms22158049.
Hypothalamic dysfunction is an initial event following diet-induced obesity, primarily involving areas regulating energy balance such as arcuate nucleus (Arc) and median eminence (ME). To gain insights into the early hypothalamic diet-induced alterations, adult CD1 mice fed a high-fat diet (HFD) for 6 weeks were studied and compared with normo-fed controls. Transmission and scanning electron microscopy and histological staining were employed for morphological studies of the ME, while Raman spectroscopy was applied for the biochemical analysis of the Arc-ME complex. In HFD mice, ME β2-tanycytes, glial cells dedicated to blood-liquor crosstalk, exhibited remarkable ultrastructural anomalies, including altered alignment, reduced junctions, degenerating organelles, and higher content of lipid droplets, lysosomes, and autophagosomes. Degenerating tanycytes also displayed an electron transparent cytoplasm filled with numerous vesicles, and they were surrounded by dilated extracellular spaces extending up to the subependymal layer. Consistently, Raman spectroscopy analysis of the Arc-ME complex revealed higher glycogen, collagen, and lipid bands in HFD mice compared with controls, and there was also a higher band corresponding to the cyanide group in the former compared to the last. Collectively, these data show that ME β-tanycytes exhibit early structural and chemical alterations due to HFD and reveal for the first-time hypothalamic cyanide presence following high dietary lipids consumption, which is a novel aspect with potential implications in the field of obesity.
下丘脑功能障碍是饮食诱导肥胖后的初始事件，主要涉及调节能量平衡的区域，如弓状核（Arc）和正中隆起（ME）。为了深入了解早期下丘脑饮食诱导的改变，研究了喂食高脂肪饮食（HFD）6 周的成年 CD1 小鼠，并与正常喂养的对照组进行了比较。透射和扫描电子显微镜以及组织学染色用于 ME 的形态学研究，而拉曼光谱则用于 Arc-ME 复合物的生化分析。在 HFD 小鼠中，ME 的 β2-分泌细胞，专门用于血液-脑脊液交流的神经胶质细胞，表现出明显的超微结构异常，包括排列改变、连接减少、细胞器退化以及脂滴、溶酶体和自噬体含量增加。退化的分泌细胞还显示出充满大量囊泡的电子透明细胞质，并且它们被延伸到室下层的扩张细胞外空间所包围。一致地，Arc-ME 复合物的拉曼光谱分析显示 HFD 小鼠的糖原、胶原蛋白和脂质带高于对照组，并且前者中与氰化物基团对应的带也高于后者。总之，这些数据表明，由于 HFD，ME 的 β-分泌细胞表现出早期的结构和化学改变，并首次揭示了高膳食脂质摄入后下丘脑氰化物的存在，这是肥胖领域的一个新方面，具有潜在的意义。
