Abstract
Hypothalamic astrocytes are particularly affected by energy-dense food consumption. How the anatomical location of these glial cells and their spatial molecular distribution in the arcuate nucleus of the hypothalamus (ARC) determine the cellular response to a high caloric diet remains unclear. In this study, we investigated their distinctive molecular responses following exposure to a high-fat high-sugar (HFHS) diet, specifically in the ARC. Using RNA sequencing and proteomics, we showed that astrocytes have a distinct transcriptomic and proteomic profile dependent on their anatomical location, with a major proteomic reprogramming in hypothalamic astrocytes. By ARC single-cell sequencing, we observed that a HFHS diet dictates time- and cell- specific transcriptomic responses, revealing that astrocytes have the most distinct regulatory pattern compared to other cell types. Lastly, we topographically and molecularly characterized astrocytes expressing glial fibrillary acidic protein and/or aldehyde dehydrogenase 1 family member L1 in the ARC, of which the abundance was significantly increased, as well as the alteration in their spatial and molecular profiles, with a HFHS diet. Together, our results provide a detailed multi-omics view on the spatial and temporal changes of astrocytes particularly in the ARC during different time points of adaptation to a high calorie diet.
Item Type: | Journal article |
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Faculties: | Medicine Medicine > Munich Cluster for Systems Neurology (SyNergy) |
Subjects: | 600 Technology > 610 Medicine and health |
ISSN: | 0894-1491 |
Language: | English |
Item ID: | 115340 |
Date Deposited: | 02. Apr 2024 08:13 |
Last Modified: | 17. Jan 2025 07:49 |
DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198 |
DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 237267101 |