Deficiency of Tristetraprolin Triggers Hyperthermia through Enhancing Hypothalamic Inflammation
Tristetraprolin (TTP), an RNA-binding protein, controls the stability of RNA by capturing AU-rich elements on their target genes. It has recently been identified that TTP serves as an anti-inflammatory protein by guiding the unstable mRNAs of pro-inflammatory proteins in multiple cells. However, it...
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MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/7/3328 |
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| author | Da Yeon Jeong Nuri Song Hye Rim Yang Thai Hien Tu Byong Seo Park Hara Kang Jeong Woo Park Byung Ju Lee Sunggu Yang Jae Geun Kim |
| author_facet | Da Yeon Jeong Nuri Song Hye Rim Yang Thai Hien Tu Byong Seo Park Hara Kang Jeong Woo Park Byung Ju Lee Sunggu Yang Jae Geun Kim |
| author_sort | Da Yeon Jeong |
| collection | DOAJ |
| description | Tristetraprolin (TTP), an RNA-binding protein, controls the stability of RNA by capturing AU-rich elements on their target genes. It has recently been identified that TTP serves as an anti-inflammatory protein by guiding the unstable mRNAs of pro-inflammatory proteins in multiple cells. However, it has not yet been investigated whether TTP affects the inflammatory responses in the hypothalamus. Since hypothalamic inflammation is tightly coupled to the disturbance of energy homeostasis, we designed the current study to investigate whether TTP regulates hypothalamic inflammation and thereby affects energy metabolism by utilizing TTP-deficient mice. We observed that deficiency of TTP led to enhanced hypothalamic inflammation via stimulation of a variety of pro-inflammatory genes. In addition, microglial activation occurred in the hypothalamus, which was accompanied by an enhanced inflammatory response. In line with these molecular and cellular observations, we finally confirmed that deficiency of TTP results in elevated core body temperature and energy expenditure. Taken together, our findings unmask novel roles of hypothalamic TTP on energy metabolism, which is linked to inflammatory responses in hypothalamic microglial cells. |
| first_indexed | 2024-03-10T12:56:28Z |
| format | Article |
| id | doaj.art-bcfd2783ec2a46a6a36672952ae92886 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:56:28Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bcfd2783ec2a46a6a36672952ae928862023-11-21T11:51:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01227332810.3390/ijms22073328Deficiency of Tristetraprolin Triggers Hyperthermia through Enhancing Hypothalamic InflammationDa Yeon Jeong0Nuri Song1Hye Rim Yang2Thai Hien Tu3Byong Seo Park4Hara Kang5Jeong Woo Park6Byung Ju Lee7Sunggu Yang8Jae Geun Kim9Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, KoreaDivision of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, KoreaDivision of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, KoreaDivision of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, KoreaDivision of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, KoreaDivision of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, KoreaDepartment of Biological Science, University of Ulsan, Ulsan 44610, KoreaDepartment of Biological Science, University of Ulsan, Ulsan 44610, KoreaDepartment of Nano-Bioengineering, Incheon National University, Incheon 22012, KoreaDivision of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, KoreaTristetraprolin (TTP), an RNA-binding protein, controls the stability of RNA by capturing AU-rich elements on their target genes. It has recently been identified that TTP serves as an anti-inflammatory protein by guiding the unstable mRNAs of pro-inflammatory proteins in multiple cells. However, it has not yet been investigated whether TTP affects the inflammatory responses in the hypothalamus. Since hypothalamic inflammation is tightly coupled to the disturbance of energy homeostasis, we designed the current study to investigate whether TTP regulates hypothalamic inflammation and thereby affects energy metabolism by utilizing TTP-deficient mice. We observed that deficiency of TTP led to enhanced hypothalamic inflammation via stimulation of a variety of pro-inflammatory genes. In addition, microglial activation occurred in the hypothalamus, which was accompanied by an enhanced inflammatory response. In line with these molecular and cellular observations, we finally confirmed that deficiency of TTP results in elevated core body temperature and energy expenditure. Taken together, our findings unmask novel roles of hypothalamic TTP on energy metabolism, which is linked to inflammatory responses in hypothalamic microglial cells.https://www.mdpi.com/1422-0067/22/7/3328tristetraprolinhypothalamusinflammationmicrogliasickness responsehyperthermia |
| spellingShingle | Da Yeon Jeong Nuri Song Hye Rim Yang Thai Hien Tu Byong Seo Park Hara Kang Jeong Woo Park Byung Ju Lee Sunggu Yang Jae Geun Kim Deficiency of Tristetraprolin Triggers Hyperthermia through Enhancing Hypothalamic Inflammation International Journal of Molecular Sciences tristetraprolin hypothalamus inflammation microglia sickness response hyperthermia |
| title | Deficiency of Tristetraprolin Triggers Hyperthermia through Enhancing Hypothalamic Inflammation |
| title_full | Deficiency of Tristetraprolin Triggers Hyperthermia through Enhancing Hypothalamic Inflammation |
| title_fullStr | Deficiency of Tristetraprolin Triggers Hyperthermia through Enhancing Hypothalamic Inflammation |
| title_full_unstemmed | Deficiency of Tristetraprolin Triggers Hyperthermia through Enhancing Hypothalamic Inflammation |
| title_short | Deficiency of Tristetraprolin Triggers Hyperthermia through Enhancing Hypothalamic Inflammation |
| title_sort | deficiency of tristetraprolin triggers hyperthermia through enhancing hypothalamic inflammation |
| topic | tristetraprolin hypothalamus inflammation microglia sickness response hyperthermia |
| url | https://www.mdpi.com/1422-0067/22/7/3328 |
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