• Introduction
  • Summary of main findings
  • Overview
• Data and analysis
• License
• References

Introduction

We provide a detailed multi-omics view of the spatial and temporal changes of different astrocyte populations in response to a high-fat high-sugar diet. Using a combination of proteomics, RNAseq, and scRNAseq data and their integrated analysis, together with in vivo labeling of astrocyte-specific molecular markers, we show that the anatomical location of astrocytes determines the cellular response to exposure to a high-caloric diet. Specifically, our results identify a high sensitivity and strong molecular response of astrocytes located in the arcuate nucleus of the hypothalamus upon exposure to a hypercaloric diet.

Summary of main findings

• Long-term exposure to a hypercaloric diet differently affects the transcriptional pattern of astrocytes located in the cortex, hippocampus, and hypothalamus, with the most prominent changes in the proteomic profile of hypothalamic astrocytes.
• Unlike other cell types in the ARC, astrocytes rapidly respond to a hypercaloric diet with a remarkable, yet transient, transcriptional activation.
• The number of astrocytes expressing the astrocytic markers Aldh1L1 and GFAP increases upon a high-fat, high-sugar (HFHS) diet feeding in a intraregional and time-dependent manner.
• The spatial location of Aldh1L1- and GFAP-expressing astrocytes in the ARC undergoes a dynamic reorganization in response to hypercaloric diet.

Overview

Since the central nervous system’s regulation of metabolism relies heavily on functional interactions between hypothalamic astrocytes and neurons, our findings on the rapid and selective astrocytic changes induced by a hypercaloric diet—occurring before significant alterations in body weight, inflammation, or insulin sensitivity—are particularly noteworthy. We provide a comprehensive multi-omics data collection on astrocytes and other cell types during different time points of the initial adaptation to a high-calorie diet to better understand the cellular circuitries acting in the ARC and their rearrangements in response to the HFHS diet. Our spatial point pattern analysis method advances cell analysis in various disciplines and experimental setups, helping to describe anatomy at a cellular level.

Data and analysis

All the data required for performing the analysis and publishing in the reference articles will soon be deposited in the National Center for Biotechnology Information Gene Expression Omnibus (GEO) and are accessible through the GEO Series accession numbers:

Data type	Link to the data	Notebook
Transcriptomics	GSE205313	transcriptomics_analysis_v1.ipynb
Proteomics	ProtData	proteomics_analysis_v1.ipynb
Singel-Cell RNA-Seq	GSE205667	astrocyte_scRNAseq_cluster_approach.ipynb
Astrocyte spatial point patterns	ASPP_data	Csppa_analysis.ipynb

To access one of the data sets, for instance, GSE78279, run the code below. Unpacking the data requires tar and gunzip, which should already be available on most systems.

cd ../  #To get to the main GitHub repo folder
mkdir -p data/AstrocytesHeterogenityARC/
cd data/AstrocytesHeterogenityARC/
wget ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE78nnn/GSE78279/suppl/GSE78279_RAW.tar
mkdir GSE78279_RAW
tar -C GSE78279_RAW -xvf GSE78279_RAW.tar
gunzip GSE78279_RAW/*_Regional_*

License

AstrocytesHeterogenityARC is distributed under the MIT license. Please read the license for __AstrocytesHeterogenityARC__distributed in the LICENSE file.

References

Publications related to AstrocytesHeterogenityARC include:

• Lutomska, L.M. *, Miok, V. *, Krahmer, N., González García, I., Gruber, T., Le Thuc, O., De Bernardis Murat, C., Legutko, B., Sterr, M., Saher, G., Lickert, H., Ussar, S., Tschöp, M., Lutter, D., García-Cáceres, C. (2022), Diet triggers specific responses of hypothalamic astrocytes in time and region dependent manner, Glia 70 (10), 1795-2008.

• Lutomska, L.M. *, Miok, V. *, Krahmer, N., González García, I., Gruber, T., Le Thuc, O., De Bernardis Murat, C., Legutko, B., Sterr, M., Saher, G., Lickert, H., Ussar, S., Tschöp, M., Lutter, D., García-Cáceres, C.(2021), Hypercaloric diet selectively triggers a transient molecular rearrangement of astrocytes in the arcuate nucleus, bioRxiv, 4(1).

Please cite the publication if you use AstrocytesHeterogenityARC.