| First Author | Wang BL | Year | 2019 |
| Journal | Xenobiotica | Volume | 49 |
| Issue | 5 | Pages | 591-601 |
| PubMed ID | 29737914 | Mgi Jnum | J:318493 |
| Mgi Id | MGI:6859873 | Doi | 10.1080/00498254.2018.1467065 |
| Citation | Wang BL, et al. (2019) Lipidomics reveal aryl hydrocarbon receptor (Ahr)-regulated lipid metabolic pathway in alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis. Xenobiotica 49(5):591-601 |
| abstractText | 1. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry (UPLC-ESI-QTOF MS)-based lipidomics was employed to elucidate new mechanism of alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis in mice. 2. Multiple lipid components significantly increased in ANIT-induced intrahepatic cholestasis, including PC 16:0, 20:4, PC 16:0, 22:6, PC 16:0, 18:2, LPC 18:2, PC 18:2, LPC 18:1, PC 18:1, 14:0, SM 18:1, 16:0, oleoylcarnitine and palmitoylcarnitine. This alteration of lipid profile was induced by the changed expression of genes choline kinase (Chk) a, sphingomyelin phosphodiesterase (SMPD) and stearoyl-coenzyme A desaturase 1 (SCD1). 3. Knockout of aryl hydrocarbon receptor (Ahr) in mice can significantly reverse ANIT-induced intrahepatic cholestasis, as indicated by lowered ALT, AST and ALP activity, and liver histology. Aryl hydrocarbon receptor knockout significantly reversed ANIT-induced lipid metabolism alteration through regulating the expression of Chka. 4. In conclusion, this study demonstrated ANIT-induced lipid metabolism disruption might be the potential pathogenesis of ANIT-induced intrahepatic cholestasis in mice. |
