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Status |
Public on Aug 05, 2023 |
Title |
Deficiency of hypothalamic taste receptor type 1 member 3 prevents western diet-induced anxiety in mice |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Accumulating studies support that the western diet (WD), a diet comprised of saturated fat and sugary drinks, contributes to the pathogenesis of anxiety disorders, the most prevalent mental disorders worldwide. However, the underlying mechanisms by which WD causes anxiety, remain unclear. Abundant expression of taste receptor type 1 member 3 (TAS1R3) is identified in the hypothalamus, a key brain area involved in both sensing peripheral nutritional signals and regulating anxiety. Thus, we investigated the role of the hypothalamic TAS1R3 in WD-induced anxiety using wild-type (WT) and Tas1r3 deficient (Tas1r3-/-) mice fed a normal diet (ND) or WD for 12 weeks. We evaluated anxiety levels with the open field test and the elevated plus maze test. Behavior tests showed WD increased anxiety in WT mice, whereas Tas1r3-/- mice were protected from WD-induced anxiety. Analyzing the hypothalamic transcriptome of WD-fed WT and Tas1r3-/- mice, we found 1,437 genes significantly regulated by Tas1r3 deficiency. In addition, bioinformatic analysis revealed that CREB-mediated maintenance of neuronal regeneration, which can prevent the development of anxiety, was enhanced in WD-fed Tas1r3-/- mice compared to WD-fed WT mice. In addition, in vitro studies further confirmed that Tas1r3 knockdown prevented suppression of CREB caused by high levels of glucose, fructose, and palmitic acid in adult hypothalamic neuronal cells. These results imply that TAS1R3 may play a key role in WD-induced alterations in hypothalamic functions, and inhibition of TAS1R3 overactivation in the hypothalamus could offer therapeutic targets to alleviate the effects of the WD on anxiety.
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Overall design |
Comparative gene expression profiling analysis of RNA-seq data for hypothalamus of western diet fed wild-type and western diet fed Tas1r3-/- mice.
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Contributor(s) |
Song J, Shon W, Shin D |
Citation(s) |
37926812 |
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Submission date |
Oct 19, 2022 |
Last update date |
Dec 01, 2023 |
Contact name |
Jaewon Song |
E-mail(s) |
sjw9509@gmail.com
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Organization name |
Seoul National University
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Street address |
Gwanak-gu
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City |
Seoul |
ZIP/Postal code |
08826 |
Country |
South Korea |
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Platforms (1) |
GPL18635 |
Ion Torrent Proton (Mus musculus) |
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Samples (4)
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Relations |
BioProject |
PRJNA891954 |
Supplementary file |
Size |
Download |
File type/resource |
GSE216063_RAW.tar |
890.0 Kb |
(http)(custom) |
TAR (of TXT) |
GSE216063_TAS1R3KO_hypothalamus_raw_gene_counts_matrix.txt.gz |
538.1 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
Processed data are available on Series record |
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