Abstract：
:Pregnane X receptor (PXR) is highly expressed in the liver and plays an integral role in the control of xenobiotic and endobiotic metabolism to maintain homeostasis. We previously reported that activation of PXR significantly induced liver enlargement. But the lipid profiling during PXR-induced hepatomegaly remains unclear. This study aimed to characterize the effect of PXR activation on hepatic lipid homeostasis by lipidomics analysis. Mice were intraperitoneally administered with the typical mPXR agonist, pregnenolone 16α-carbonitrile (PCN, 100 mg/kg/d), for 5 days. Liver and serum were collected for further analysis. The results confirmed that PXR activation can significantly induce liver enlargement. An obvious hepatic lipid accumulation was observed in PCN-treated mice, as determined by H&E and Oil Red O staining. Ultra-high performance liquid chromatography-Q Exactive Orbitrap high-resolution mass spectrometer (UHPLC-Q Exactive Orbitrap HRMS)-based lipidomics was performed to characterize the change in lipid species. A total of 20 potential lipid biomarkers were significantly perturbed. The most significant change was found in the triacylglycerol (TG), which constituted with the lower number of carbon atoms and double bonds. Moreover, the mRNA expression levels showed that PCN-induced PXR activation significantly regulated the expression of genes involved in the uptake, synthesis and metabolism of TG, which was consistent with increased TG levels. Collectively, these findings demonstrated that lipids such as TG were significantly accumulated during PXR-induced hepatomegaly.
journal_name
J Pharm Biomed Analjournal_title
Journal of pharmaceutical and biomedical analysisauthors
Jiang Y,Yao X,Fan S,Gao Y,Zhang H,Huang M,Bi Hdoi
10.1016/j.jpba.2020.113851subject
Has Abstractpub_date
2021-02-20 00:00:00pages
113851eissn
0731-7085issn
1873-264Xpii
S0731-7085(20)31738-6journal_volume
195pub_type
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