Taste receptor type 1 member 3 enables western diet-induced anxiety in mice
Abstract Background Accumulating evidence supports that the Western diet (WD), a diet high in saturated fat and sugary drinks, contributes to the pathogenesis of anxiety disorders, which are the most prevalent mental disorders worldwide. However, the underlying mechanisms by which WD causes anxiety...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | BMC Biology |
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| Online Access: | https://doi.org/10.1186/s12915-023-01723-x |
| _version_ | 1797629995567284224 |
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| author | Jae Won Song Keon-Hee Lee Hobin Seong Dong-Mi Shin Woo-Jeong Shon |
| author_facet | Jae Won Song Keon-Hee Lee Hobin Seong Dong-Mi Shin Woo-Jeong Shon |
| author_sort | Jae Won Song |
| collection | DOAJ |
| description | Abstract Background Accumulating evidence supports that the Western diet (WD), a diet high in saturated fat and sugary drinks, contributes to the pathogenesis of anxiety disorders, which are 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) has been identified in the hypothalamus, a key brain area involved in sensing peripheral nutritional signals and regulating anxiety. Thus, we investigated the influence of excessive WD intake on anxiety and mechanisms by which WD intake affects anxiety development using wild-type (WT) and Tas1r3 deficient (Tas1r3 −/−) mice fed a normal diet (ND) or WD for 12 weeks. Results WD increased anxiety in male WT mice, whereas male Tas1r3 −/− mice were protected from WD-induced anxiety, as assessed by open field (OF), elevated plus maze (EPM), light–dark box (LDB), and novelty-suppressed feeding (NSF) tests. Analyzing the hypothalamic transcriptome of WD-fed WT and Tas1r3 −/− mice, we found 1,432 genes significantly up- or down-regulated as a result of Tas1r3 deficiency. Furthermore, bioinformatic analysis revealed that the CREB/BDNF signaling-mediated maintenance of neuronal regeneration, which can prevent anxiety development, was enhanced in WD-fed Tas1r3 −/− mice compared with WD-fed WT mice. Additionally, in vitro studies further confirmed that Tas1r3 knockdown prevents the suppression of Creb1 and of CREB-mediated BDNF expression caused by high levels of glucose, fructose, and palmitic acid in hypothalamic neuronal cells. Conclusions Our results imply that TAS1R3 may play a key role in WD-induced alterations in hypothalamic functions, and that inhibition of TAS1R3 overactivation in the hypothalamus could offer therapeutic targets to alleviate the effects of WD on anxiety. |
| first_indexed | 2024-03-11T11:01:45Z |
| format | Article |
| id | doaj.art-f8521bf9733d44ebbffe694ff367d19e |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-03-11T11:01:45Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-f8521bf9733d44ebbffe694ff367d19e2023-11-12T12:30:15ZengBMCBMC Biology1741-70072023-11-0121111410.1186/s12915-023-01723-xTaste receptor type 1 member 3 enables western diet-induced anxiety in miceJae Won Song0Keon-Hee Lee1Hobin Seong2Dong-Mi Shin3Woo-Jeong Shon4Department of Food and Nutrition, Seoul National University College of Human EcologyDepartment of Food and Nutrition, Seoul National University College of Human EcologyDepartment of Food and Nutrition, Seoul National University College of Human EcologyDepartment of Food and Nutrition, Seoul National University College of Human EcologyDepartment of Food and Nutrition, Seoul National University College of Human EcologyAbstract Background Accumulating evidence supports that the Western diet (WD), a diet high in saturated fat and sugary drinks, contributes to the pathogenesis of anxiety disorders, which are 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) has been identified in the hypothalamus, a key brain area involved in sensing peripheral nutritional signals and regulating anxiety. Thus, we investigated the influence of excessive WD intake on anxiety and mechanisms by which WD intake affects anxiety development using wild-type (WT) and Tas1r3 deficient (Tas1r3 −/−) mice fed a normal diet (ND) or WD for 12 weeks. Results WD increased anxiety in male WT mice, whereas male Tas1r3 −/− mice were protected from WD-induced anxiety, as assessed by open field (OF), elevated plus maze (EPM), light–dark box (LDB), and novelty-suppressed feeding (NSF) tests. Analyzing the hypothalamic transcriptome of WD-fed WT and Tas1r3 −/− mice, we found 1,432 genes significantly up- or down-regulated as a result of Tas1r3 deficiency. Furthermore, bioinformatic analysis revealed that the CREB/BDNF signaling-mediated maintenance of neuronal regeneration, which can prevent anxiety development, was enhanced in WD-fed Tas1r3 −/− mice compared with WD-fed WT mice. Additionally, in vitro studies further confirmed that Tas1r3 knockdown prevents the suppression of Creb1 and of CREB-mediated BDNF expression caused by high levels of glucose, fructose, and palmitic acid in hypothalamic neuronal cells. Conclusions Our results imply that TAS1R3 may play a key role in WD-induced alterations in hypothalamic functions, and that inhibition of TAS1R3 overactivation in the hypothalamus could offer therapeutic targets to alleviate the effects of WD on anxiety.https://doi.org/10.1186/s12915-023-01723-xAnxiety disordersWestern dietTaste receptor type 1 member 3Hypothalamus |
| spellingShingle | Jae Won Song Keon-Hee Lee Hobin Seong Dong-Mi Shin Woo-Jeong Shon Taste receptor type 1 member 3 enables western diet-induced anxiety in mice BMC Biology Anxiety disorders Western diet Taste receptor type 1 member 3 Hypothalamus |
| title | Taste receptor type 1 member 3 enables western diet-induced anxiety in mice |
| title_full | Taste receptor type 1 member 3 enables western diet-induced anxiety in mice |
| title_fullStr | Taste receptor type 1 member 3 enables western diet-induced anxiety in mice |
| title_full_unstemmed | Taste receptor type 1 member 3 enables western diet-induced anxiety in mice |
| title_short | Taste receptor type 1 member 3 enables western diet-induced anxiety in mice |
| title_sort | taste receptor type 1 member 3 enables western diet induced anxiety in mice |
| topic | Anxiety disorders Western diet Taste receptor type 1 member 3 Hypothalamus |
| url | https://doi.org/10.1186/s12915-023-01723-x |
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