Lipidomics reveal aryl hydrocarbon receptor (Ahr)-regulated lipid metabolic pathway in alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis

Abstract

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.

Keywords:

• Intrahepatic cholestasis
• alpha-naphthyl isothiocyanate (ANIT)
• lipidomics
• aryl hydrocarbon receptor (Ahr)

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the project for the National Key Research and Development Program (2016YFC0903100, 2016YFC0903102), the 13^th Five Year Plan and TMU Talent Project (11601501/2016KJ0313), National Natural Science Foundation of China (No. 81602826, 81672961), Individualized Diagnosis and Treatment of Colorectal Cancer (No. LNCCC-B05-2015), Foundation of Committee on Science and Technology of Tianjin (Grant No. 15JCYBJC54700), the China Postdoctoral Science Foundation (2016M590210), Tianjin Health Bureau Science Foundation Key Project (16KG154) and Tianjin Project of Thousand Youth Talents.