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DOI | 10.1038/s41467-019-11943-x |
AhR and SHP regulate phosphatidylcholine and S-adenosylmethionine levels in the one-carbon cycle | |
Kim, Young-Chae1; Seok, Sunmi1; Byun, Sangwon1; Kong, Bo2; Zhang, Yang3,4; Guo, Grace2; Xie, Wen5; Ma, Jian3,4; Kemper, Byron1; Kemper, Jongsook Kim1 | |
2019-09-09 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Phosphatidylcholines (PC) and S-adenosylmethionine (SAM) are critical determinants of hepatic lipid levels, but how their levels are regulated is unclear. Here, we show that Pemt and Gnmt, key one-carbon cycle genes regulating PC/SAM levels, are downregulated after feeding, leading to decreased PC and increased SAM levels, but these effects are blunted in small heterodimer partner (SHP)-null or FGF15-null mice. Further, aryl hydrocarbon receptor (AhR) is translocated into the nucleus by insulin/PKB signaling in the early fed state and induces Pemt and Gnmt expression. This induction is blocked by FGF15 signaling-activated SHP in the late fed state. Adenoviral-mediated expression of AhR in obese mice increases PC levels and exacerbates steatosis, effects that are blunted by SHP co-expression or Pemt downregulation. PEMT, AHR, and PC levels are elevated in simple steatosis patients, but PC levels are robustly reduced in steatohepatitis-fibrosis patients. This study identifies AhR and SHP as new physiological regulators of PC/SAM levels. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000424318100004 |
WOS关键词 | ARYL-HYDROCARBON RECEPTOR ; FATTY LIVER-DISEASE ; SMALL HETERODIMER PARTNER ; BILE-ACID SYNTHESIS ; NEGATIVE FEEDBACK-REGULATION ; FARNESOID X RECEPTOR ; HEPATIC STEATOSIS ; SIGNALING PATHWAYS ; INSULIN-RESISTANCE ; SENSITIZES MICE |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204529 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA; 2.Rutgers State Univ, Dept Pharmacol & Toxicol, Sch Pharm, Piscataway, NJ 08854 USA; 3.Carnegie Melon Univ, Dept Computat, Sch Comp Sci, Pittsburgh, PA 15213 USA; 4.Carnegie Melon Univ, Comparat Genom Lab, Sch Comp Sci, Pittsburgh, PA 15213 USA; 5.Univ Pittsburgh, Dept Pharmaceut Sci, Sch Pharm, Pittsburgh, PA 15261 USA |
推荐引用方式 GB/T 7714 | Kim, Young-Chae,Seok, Sunmi,Byun, Sangwon,et al. AhR and SHP regulate phosphatidylcholine and S-adenosylmethionine levels in the one-carbon cycle[J]. NATURE COMMUNICATIONS,2019,9. |
APA | Kim, Young-Chae.,Seok, Sunmi.,Byun, Sangwon.,Kong, Bo.,Zhang, Yang.,...&Kemper, Jongsook Kim.(2019).AhR and SHP regulate phosphatidylcholine and S-adenosylmethionine levels in the one-carbon cycle.NATURE COMMUNICATIONS,9. |
MLA | Kim, Young-Chae,et al."AhR and SHP regulate phosphatidylcholine and S-adenosylmethionine levels in the one-carbon cycle".NATURE COMMUNICATIONS 9(2019). |
条目包含的文件 | 条目无相关文件。 |
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