Diet triggers specific responses of hypothalamic astrocytes in time and region dependent manner

Lutomska, Luiza Maria; Miok, Viktorian; Krahmer, Natalie; Garcia, Ismael Gonzalez; Gruber, Tim; Le Thuc, Ophelia; Murat, Cahue D. B.; Legutko, Beata; Sterr, Michael; Saher, Gesine; Lickert, Heiko; Mueller, Timo D.; Ussar, Siegfried; Tschoep, Matthias H.; Lutter, Dominik und Garcia-Caceres, Cristina (2022): Diet triggers specific responses of hypothalamic astrocytes in time and region dependent manner. In: Glia, Bd. 70, Nr. 11: S. 2062-2078

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0894-1491
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 237267101