Lithocholic acid disrupts phospholipid and sphingolipid homeostasis leading to cholestasis in mice.

ABSTRACT:

Unlabelled

Lithocholic acid (LCA) is an endogenous compound associated with hepatic toxicity during cholestasis. LCA exposure in mice resulted in decreased serum lysophosphatidylcholine (LPC) and sphingomyelin levels due to elevated lysophosphatidylcholine acyltransferase (LPCAT) and sphingomyelin phosphodiesterase (SMPD) expression. Global metabolome analysis indicated significant decreases in serum palmitoyl-, stearoyl-, oleoyl-, and linoleoyl-LPC levels after LCA exposure. LCA treatment also resulted in decreased serum sphingomyelin levels and increased hepatic ceramide levels, and induction of LPCAT and SMPD messenger RNAs (mRNAs). Transforming growth factor-β (TGF-β) induced Lpcat2/4 and Smpd3 gene expression in primary hepatocytes and the induction was diminished by pretreatm

SUBMITTER: Matsubara T 

PROVIDER: S-EPMC3077083 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature