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Lipidomics Revealed Idiopathic Pulmonary Fibrosis-Induced Hepatic Lipid Disorders Corrected with Treatment of Baicalin in a Murine Model

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Abstract

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease. The current standard treatment with glucocorticoids (GCs) leads to many adverse effects, and its effectiveness is questionable. Thus, it is critical and urgent to find new drug(s) for treatment of IPF. Baicalin (BAI) is an attractive candidate for this purpose. Herein, utilizing shotgun lipidomics, we revealed that IPF could lead to a lipid disorder of the liver in an animal model induced by bleomycin and confirmed through histopathological studies of the lung. Lipidomics further demonstrated that this disorder could virtually be corrected after treatment with BAI, but not with dexamethasone (DEX) (a commonly used GC for treatment of IPF). In contrast, the treatment with DEX did not improve IPF but led to tremendous alterations in hepatic lipidomes and accumulation of fat in the liver, which was very different from the lipid disorder induced by IPF. The underpinning mechanisms of the IPF-resultant lipid disorder and DEX-induced lipotoxicity as revealed by shotgun lipidomics were extensively discussed. Taken together, the current study showed that IPF could lead to hepatic lipid disorder, which can be treated with BAI, and demonstrated that lipidomics could be a powerful tool for drug screening.

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Abbreviations

BAI:

Baicalin

BLM:

Bleomycin

Cer:

Ceramide

CL:

Cardiolipin

CDP:

Cytidine diphosphate

DAG:

Diacylglycerol

DEX:

Dexamethasone

GCs:

Glucocorticoids

IPF:

Idiopathic pulmonary fibrosis

MDMS-SL:

Multidimensional mass spectrometry-based shotgun lipidomics

MLCL:

Monolysocardiolipin

MS:

Mass spectrometry or mass spectrometric

PA:

Phosphatidic acid

PC:

Phosphatidylcholine

PE:

Phosphatidylethanolamine

PG:

Phosphatidylglycerol

PI:

Phosphatidylinositol

PS:

Phosphatidylserine

SM:

Sphingomyelin

TAG:

Triacylglycerol

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Acknowledgments

We thank Dr. Miao Wang at Sanford-Burnham Medical Research Institute for his technical help. This work was supported by the Natural Science Foundation of Zhejiang Chinese Medical University (No. 711200F002) to C.H., the Natural Science Foundation of Zhejiang Province of China (No. LQ12H28004) to Y.W., a program sponsored by Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents to C.W., and the National Basic Research Program “973” of China (No. 2014CB5430) to Y.F.

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    Authors and Affiliations

    1. College of Basic Medical Sciences, Zhejiang Chinese Medical University, 548 Bingwen Road, Hangzhou, Zhejiang, 310053, China

      Changfeng Hu, Yongsheng Fan, Haichang Li, Jida Zhang, Xianlin Han & Chengping Wen

    2. Department of Pharmacy, Zhejiang Chinese Medical University, 548 Bingwen Road, Hangzhou, Zhejiang, 310053, China

      Yiqi Wang & Shuijuan Zhang

    3. Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, 6400 Sanger Road, Orlando, Florida, 32827, USA

      Chunyan Wang & Xianlin Han

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    1. Changfeng Hu
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    Changfeng Hu and Yiqi Wang contributed equally to this work.

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    Hu, C., Wang, Y., Fan, Y. et al. Lipidomics Revealed Idiopathic Pulmonary Fibrosis-Induced Hepatic Lipid Disorders Corrected with Treatment of Baicalin in a Murine Model. AAPS J 17, 711–722 (2015). https://doi.org/10.1208/s12248-014-9714-4

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