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- Publisher Website: 10.1016/j.jhep.2012.10.022
- Scopus: eid_2-s2.0-84872388467
- PMID: 23108115
- WOS: WOS:000315069900023
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Article: Pharmacological inhibition of adipocyte fatty acid binding protein alleviates both acute liver injury and non-alcoholic steatohepatitis in mice
Title | Pharmacological inhibition of adipocyte fatty acid binding protein alleviates both acute liver injury and non-alcoholic steatohepatitis in mice |
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Authors | |
Keywords | Non-alcoholic steatohepatitis Kupffer cells Inflammation Obesity |
Issue Date | 2013 |
Publisher | Elsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep |
Citation | Journal of Hepatology, 2013, v. 58 n. 2, p. 358-364 How to Cite? |
Abstract | Background & Aims: Adipocyte fatty acid binding protein (A-FABP) is a key mediator of inflammatory response in macrophages. Increased hepatic expression and circulating levels of A-FABP have been observed in patients with non-alcoholic fatty liver disease (NAFLD). Here, we investigated the role of A-FABP in both lipopolysaccaride (LPS)-induced acute liver injury and high fat high cholesterol (HFHC) diet-induced NAFLD in mice. Methods: Mice with LPS-induced acute liver injury and HFHC diet-induced obesity were treated with the A-FABP inhibitor BMS309403. Liver tissues of the mice were analyzed by immunohistochemistry, Western blot or real-time PCR. Results: A-FABP expression in Kupffer cells was significantly elevated in mice with LPS-induced acute liver injury and HFHC diet-induced obesity, as compared to their healthy controls. Pretreatment of mice with BMS309403 led to a diminished LPS-induced elevation in serum levels of alanine transaminase and hepatic production of pro-inflammatory cytokines. Likewise, chronic treatment of HFHC diet-induced obese mice with BMS309403 ameliorated hepatic steatosis, macrophage infiltration, and cellular ballooning of hepatocytes. Such improvements in liver function and morphology were accompanied by significantly decreased activation of both c-Jun and NF-κB. Pretreatment with BMS309403 suppressed both LPS- and palmitate-induced pro-inflammatory responses in isolated rat Kupffer cells. Adenovirus-mediated ectopic expression of A-FABP alone was sufficient to induce liver injury and inflammation in mice. Conclusions: These findings suggest that A-FABP is an important contributor to both LPS-induced acute liver injury and diet-induced NAFLD by potentiating inflammation in Kupffer cells. Pharmacological inhibition of A-FABP may represent a promising modality for obesity-related non-alcoholic steatohepatitis. © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. |
Persistent Identifier | http://hdl.handle.net/10722/181060 |
ISSN | 2023 Impact Factor: 26.8 2023 SCImago Journal Rankings: 9.857 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Hoo, RLC | en_US |
dc.contributor.author | Lee, PC | en_US |
dc.contributor.author | Zhou, M | en_US |
dc.contributor.author | Wong, YL | en_US |
dc.contributor.author | Hui, X | en_US |
dc.contributor.author | Xu, A | en_US |
dc.contributor.author | Lam, KSL | en_US |
dc.date.accessioned | 2013-02-19T11:32:49Z | - |
dc.date.available | 2013-02-19T11:32:49Z | - |
dc.date.issued | 2013 | en_US |
dc.identifier.citation | Journal of Hepatology, 2013, v. 58 n. 2, p. 358-364 | en_US |
dc.identifier.issn | 0168-8278 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/181060 | - |
dc.description.abstract | Background & Aims: Adipocyte fatty acid binding protein (A-FABP) is a key mediator of inflammatory response in macrophages. Increased hepatic expression and circulating levels of A-FABP have been observed in patients with non-alcoholic fatty liver disease (NAFLD). Here, we investigated the role of A-FABP in both lipopolysaccaride (LPS)-induced acute liver injury and high fat high cholesterol (HFHC) diet-induced NAFLD in mice. Methods: Mice with LPS-induced acute liver injury and HFHC diet-induced obesity were treated with the A-FABP inhibitor BMS309403. Liver tissues of the mice were analyzed by immunohistochemistry, Western blot or real-time PCR. Results: A-FABP expression in Kupffer cells was significantly elevated in mice with LPS-induced acute liver injury and HFHC diet-induced obesity, as compared to their healthy controls. Pretreatment of mice with BMS309403 led to a diminished LPS-induced elevation in serum levels of alanine transaminase and hepatic production of pro-inflammatory cytokines. Likewise, chronic treatment of HFHC diet-induced obese mice with BMS309403 ameliorated hepatic steatosis, macrophage infiltration, and cellular ballooning of hepatocytes. Such improvements in liver function and morphology were accompanied by significantly decreased activation of both c-Jun and NF-κB. Pretreatment with BMS309403 suppressed both LPS- and palmitate-induced pro-inflammatory responses in isolated rat Kupffer cells. Adenovirus-mediated ectopic expression of A-FABP alone was sufficient to induce liver injury and inflammation in mice. Conclusions: These findings suggest that A-FABP is an important contributor to both LPS-induced acute liver injury and diet-induced NAFLD by potentiating inflammation in Kupffer cells. Pharmacological inhibition of A-FABP may represent a promising modality for obesity-related non-alcoholic steatohepatitis. © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. | - |
dc.language | eng | en_US |
dc.publisher | Elsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep | en_US |
dc.relation.ispartof | Journal of Hepatology | en_US |
dc.rights | NOTICE: this is the author’s version of a work that was accepted for publication in <Journal title>. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in PUBLICATION, [VOL#, ISSUE#, (DATE)] DOI# | en_US |
dc.subject | Non-alcoholic steatohepatitis | - |
dc.subject | Kupffer cells | - |
dc.subject | Inflammation | - |
dc.subject | Obesity | - |
dc.title | Pharmacological inhibition of adipocyte fatty acid binding protein alleviates both acute liver injury and non-alcoholic steatohepatitis in mice | en_US |
dc.type | Article | en_US |
dc.identifier.openurl | http://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0168-8278&volume=58&issue=2&spage=358&epage=364&date=2013&atitle=Pharmacological+inhibition+of+adipocyte+fatty+acid+binding+protein+alleviates+both+acute+liver+injury+and+non-alcoholic+steatohepatitis+in+mice | en_US |
dc.identifier.email | Hoo, RLC: rubyhoo@hkucc.hku.hk | en_US |
dc.identifier.email | Lee, PC: idalee@hku.hk | en_US |
dc.identifier.email | Hui, X: hannahui@hkucc.hku.hk | en_US |
dc.identifier.email | Xu, A: amxu@hkucc.hku.hk | en_US |
dc.identifier.email | Lam, KSL: ksllam@hku.hk | en_US |
dc.identifier.authority | Hoo, RLC=rp01334 | en_US |
dc.identifier.authority | Xu, A=rp00485 | en_US |
dc.identifier.authority | Lam, KSL=rp00343 | en_US |
dc.identifier.doi | 10.1016/j.jhep.2012.10.022 | - |
dc.identifier.pmid | 23108115 | - |
dc.identifier.scopus | eid_2-s2.0-84872388467 | - |
dc.identifier.hkuros | 213320 | en_US |
dc.identifier.hkuros | 228176 | - |
dc.identifier.volume | 58 | en_US |
dc.identifier.issue | 2 | en_US |
dc.identifier.spage | 358 | en_US |
dc.identifier.epage | 364 | en_US |
dc.identifier.isi | WOS:000315069900023 | - |
dc.identifier.issnl | 0168-8278 | - |