Deficiency of Tristetraprolin Triggers Hyperthermia through Enhancing Hypothalamic Inflammation

International Journal of Molecular Sciences

JeongWoo Park¹  ByungJu Lee¹  Sunggu Yang²  JaeGeun Kim³  Hara Kang³  Nuri Song³  ThaiHien Tu³  ByongSeo Park³  DaYeon Jeong³  HyeRim Yang³ 

[1] Department of Biological Science, University of Ulsan, Ulsan 44610, Korea;Department of Nano-Bioengineering, Incheon National University, Incheon 22012, Korea;Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Korea;

关键词: tristetraprolin;    hypothalamus;    inflammation;    microglia;    sickness response;    hyperthermia;   

DOI  :  10.3390/ijms22073328

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown