High-Fat Diet Impairs Mouse Median Eminence: A Study by Transmission and Scanning Electron Microscopy Coupled with Raman Spectroscopy

Abstract

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 β2-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.

The Properties and Functions of Glial Cell Types of the Hypothalamic Median Eminence

“…Fasting also induces tanycytic-VEGF expression that increases capillary fenestration in the ME and also increases permeability of the ME-ArcN barrier ( 22 ). Mice on a high-fat diet show ultrastructural changes in tanycytes including lipid accumulation, organelle degradation and reduced junction formation ( 23 ) that aligns with reports of increased permeability of the ME-CSF barrier in mice following hyperglycaemia ( 7 ). Loss of Igf1r signalling in tanycytes impairs the tanycytic ability to proliferate following injury to the ME ( 5 ) and, in terms of differential gene expression, tanycytes are the second most responsive to a fasting-refeeding paradigm in mice, after astrocytes ( 12 ).…”

Fatty Acids: An Insight into the Pathogenesis of Neurodegenerative Diseases and Therapeutic Potential

“…For example, monocytes may infiltrate the mouse brain after 15 weeks of HFD, where a correlation between the number of monocyte-derived macrophages in the brain and body weight is observed [ 94 ]. Moreover, in a study, they examine the BBB disruption in the offspring of animals fed with HFD rich in PA, resulting in the offspring of HFD-fed mice showing an increase in the BBB disruption, probably due to a reduction in the cell projections of a special type of ependymal cells called tanycytes [ 95 ]. The tanycytic cell bodies are in the third ventricle with their projections reaching the brain parenchyma, contacting the arcuate nucleus (ARC) neurons and endothelial cells in this area [ 27 ], and they form a passive physical barrier that prevents molecules in the median eminence from diffusing dorsally into the ARC [ 96 ].…”

Early Life Stress, Brain Development, and Obesity Risk: Is Oxytocin the Missing Link?

“…The chronic positive energy balance results in an excessive accumulation of lipids within the adipose depots and in different cytotypes. This phenomenon is responsible for adipose tissue expansion, inflammation, and lipotoxicity and deeply compromises several organ functions [ 7 , 10 , 11 , 12 , 13 ]. For example, obesity-related lipotoxicity and chronic inflammation may result in non-alcoholic fatty liver steatohepatitis; skeletal muscle dysfunction, i.e., sarcopenic obesity [ 12 , 14 ]; and pancreatic β-cell impairment [ 15 ].…”