title: Hepatic Induction of Fatty Acid Binding Protein 4 Plays a Pathogenic Role in Sepsis in Mice.
abstract: Sepsis is defined as the host's deleterious systemic inflammatory response to microbial infections. Herein, we report an essential role of the fatty acid binding protein 4 (FABP4; alias adipocyte protein 2 or aP2), a lipid-binding chaperone, in sepsis response. Bioinformatic analysis of the Gene Expression Omnibus data sets showed the level of FABP4 was higher in the nonsurvival sepsis patients' whole blood compared to the survival cohorts. The expression of Fabp4 was induced in a liver-specific manner in cecal ligation and puncture (CLP) and lipopolysaccharide treatment models of sepsis. The induction of Fabp4 may have played a pathogenic role, because ectopic expression of Fabp4 in the liver sensitized mice to CLP-induced inflammatory response and worsened the animal's survival. In contrast, pharmacological inhibition of Fabp4 markedly alleviated the CLP responsive inflammation and tissue damage and improved survival. We conclude that FABP4 is an important mediator of the sepsis response. Early intervention by pharmacological inhibition of FABP4 may help to manage sepsis in the clinic.
authors.affiliation: Institute of Clinical Pharmacology and Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-Sen University, Guangzhou, China; Department of Pharmaceutical Sciences, Center for Pharmacogenetics, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Bingfang
authors.initials: B
authors.lastname: Hu
authors.affiliation: Institute of Clinical Pharmacology and Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Sciences, Center for Pharmacogenetics, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Gastroenterology, Peking University People's Hospital, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutical Sciences, Center for Pharmacogenetics, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Institute of Clinical Pharmacology and Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Sciences, Center for Pharmacogenetics, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Chai
authors.affiliation: Department of Pharmaceutical Sciences, Center for Pharmacogenetics, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Meishu
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutical Sciences, Center for Pharmacogenetics, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Jiong
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Pharmaceutical Sciences, Center for Pharmacogenetics, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Peipei
authors.initials: P
authors.lastname: Lu
authors.affiliation: Department of Pharmaceutical Sciences, Center for Pharmacogenetics, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Songrong
authors.initials: S
authors.lastname: Ren
authors.affiliation: Department of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Su
authors.initials: S
authors.lastname: Zeng
authors.affiliation: Department of Pharmaceutical Sciences, Center for Pharmacogenetics, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Gastroenterology, Peking University People's Hospital, Beijing, China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Sciences, Center for Pharmacogenetics, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address: wex6@pitt.edu.
authors.forename: Wen
authors.initials: W
authors.lastname: Xie
authors.affiliation: Institute of Clinical Pharmacology and Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-Sen University, Guangzhou, China. Electronic address: huangmin@mail.sysu.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
mesh_terms: D000273:Adipose Tissue; D000818:Animals; D002432:Cecum; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000503:physiopathology; D050556:Fatty Acid-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D022781:Hepatocytes / Q000382:microbiology / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007728:Kupffer Cells / Q000502:physiology; D008026:Ligation; D008070:Lipopolysaccharides; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010868:Pimozide / Q000494:pharmacology; D011677:Punctures; D018805:Sepsis / Q000209:etiology* / Q000401:mortality
chemical_list: C493410:FABP4 protein, human; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010868:Pimozide