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Deregulation of Bile Acid Homeostasis and Lipid Metabolism in Parenteral Nutrition Mouse Model
Author(s) -
Zhan Le,
Yang Ill,
Kong Bo,
Shen Jianliang,
Buckley Brian,
Guo Grace
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.937.1
Subject(s) - cholesterol 7 alpha hydroxylase , farnesoid x receptor , bile acid , homeostasis , medicine , endocrinology , cyp8b1 , lipid metabolism , glucose homeostasis , chenodeoxycholic acid , biology , chemistry , nuclear receptor , biochemistry , gene , diabetes mellitus , transcription factor , insulin resistance
Long‐term parenteral nutrition (PN) administration can lead to PN associated liver diseases (PNALD), of which the molecular pathogenesis remains poorly understood. Animal studies in preterm piglets and several mouse models have shed light on the mechanisms underlined. To date, the roles of bile acids (BAs) and their signaling pathways involved in the development and progression of PNALD are still unclear. In the current study, we have established a mouse PN model with IV infusion of PN solution containing soybean oil based lipid emulsion. Liver mRNA profiling was determined by microarray analysis and serum BA profiling was determined by UPLC‐MS method. PN significantly decreased the mRNA levels of sterol 12‐alpha‐hydroxylase ( Cyp8b1 ) and BA efflux genes, and increased that of cholesterol 7‐alpha‐hydroxylase ( Cyp7a1 ). Consistently, both the levels and the percentages of primary BAs as well as total non‐12α‐OH BAs increased significantly in the serum of PN mice. In addition, PN increased the expression of several key genes involved in lipogenesis, which could be suppressed by farnesoid X receptor (FXR) and/or induced by liver X receptor alpha (LXRα). This study suggests that PN leads to deregulation of BA and lipid homeostasis, which predispose the subjects to pro‐cholestatic conditions. Determining deficiencies in BA pathway in patients may help to predict probability of PNALD development, and maintaining BA homeostasis by therapeutic agents may represent a novel treatment in the future for PNALD.