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AhR and SHP regulate phosphatidylcholine and S-adenosylmethionine levels in the one-carbon cycle

Author

Listed:
  • Young-Chae Kim

    (University of Illinois at Urbana-Champaign)

  • Sunmi Seok

    (University of Illinois at Urbana-Champaign)

  • Sangwon Byun

    (University of Illinois at Urbana-Champaign)

  • Bo Kong

    (Rutgers University)

  • Yang Zhang

    (Carnegie Melon University)

  • Grace Guo

    (Rutgers University)

  • Wen Xie

    (University of Pittsburgh)

  • Jian Ma

    (Carnegie Melon University)

  • Byron Kemper

    (University of Illinois at Urbana-Champaign)

  • Jongsook Kim Kemper

    (University of Illinois at Urbana-Champaign)

Abstract

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.

Suggested Citation

  • Young-Chae Kim & Sunmi Seok & Sangwon Byun & Bo Kong & Yang Zhang & Grace Guo & Wen Xie & Jian Ma & Byron Kemper & Jongsook Kim Kemper, 2018. "AhR and SHP regulate phosphatidylcholine and S-adenosylmethionine levels in the one-carbon cycle," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03060-y
    DOI: 10.1038/s41467-018-03060-y
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