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

Young Chae Kim, Sunmi Seok, Sangwon Byun, Bo Kong, Yang Zhang, Grace Guo, Wen Xie, Jian Ma, Byron Kemper, Jongsook Kim Kemper

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number540
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

carbon cycle
Carbon Cycle
Aryl Hydrocarbon Receptors
S-Adenosylmethionine
Phosphatidylcholines
Carbon
hydrocarbons
Down-Regulation
mice
Obese Mice
fibrosis
insulin
Fatty Liver
regulators
determinants
genes
Fibrosis
Genes
lipids
induction

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

AhR and SHP regulate phosphatidylcholine and S-adenosylmethionine levels in the one-carbon cycle. / Kim, Young Chae; Seok, Sunmi; Byun, Sangwon; Kong, Bo; Zhang, Yang; Guo, Grace; Xie, Wen; Ma, Jian; Kemper, Byron; Kemper, Jongsook Kim.

In: Nature communications, Vol. 9, No. 1, 540, 01.12.2018.

Research output: Contribution to journalArticle

Kim, Young Chae ; Seok, Sunmi ; Byun, Sangwon ; Kong, Bo ; Zhang, Yang ; Guo, Grace ; Xie, Wen ; Ma, Jian ; Kemper, Byron ; Kemper, Jongsook Kim. / AhR and SHP regulate phosphatidylcholine and S-adenosylmethionine levels in the one-carbon cycle. In: Nature communications. 2018 ; Vol. 9, No. 1.
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