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Article: Mitochondrial dysfunction contributes to the increased vulnerabilities of adiponectin knockout mice to liver injury

TitleMitochondrial dysfunction contributes to the increased vulnerabilities of adiponectin knockout mice to liver injury
Authors
Issue Date2008
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
Citation
Hepatology, 2008, v. 48 n. 4, p. 1087-1096 How to Cite?
AbstractAdiponectin is an adipocyte-derived hormone with a wide range of beneficial effects on obesity-related medical complications. Numerous epidemiological investigations in diverse ethnic groups have identified a lower adiponectin level as an independent risk factor for nonalcoholic fatty liver diseases and liver dysfunctions. Animal studies have demonstrated that replenishment of adiponectin protects against various forms of hepatic injuries, suggesting it to be a potential drug candidate for the treatment of liver diseases. This study was designed to investigate the cellular and molecular mechanisms underlying the hepatoprotective effects of adiponectin. Our results demonstrated that in adiponectin knockout (ADN-KO) mice, there was a preexisting condition of hepatic steatosis and mitochondrial dysfunction that might contribute to the increased vulnerabilities of these mice to secondary liver injuries induced by obesity and other conditions. Adenovirus-mediated replenishment of adiponectin depleted lipid accumulation, restored the oxidative activities of mitochondrial respiratory chain (MRC) complexes, and prevented the accumulation of lipid peroxidation products in ADN-KO mice but had no obvious effects on mitochondrial biogenesis. The gene and protein levels of uncoupling protein 2 (UCP2), a mitochondrial membrane transporter, were decreased in ADN-KO mice and could be significantly up-regulated by adiponectin treatment. Moreover, the effects of adiponectin on mitochondrial activities and on protection against endotoxin-induced liver injuries were significantly attenuated in UCP2 knockout mice. Conclusion: These results suggest that the hepatoprotective properties of adiponectin are mediated at least in part by an enhancement of the activities of MRC complexes through a mechanism involving UCP2. Copyright © 2008 by the American Association for the Study of Liver Diseases.
Persistent Identifierhttp://hdl.handle.net/10722/91446
ISSN
2015 Impact Factor: 11.711
2015 SCImago Journal Rankings: 4.752
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong ResearchHKU 778007
HKU 7645/06M
U.S. National Institutes of HealthHL-51586
Area of Excellent SchemeAoE/P-10-01
Funding Information:

Supported by grants from Seeding Funds for Basic Research of the University of Hong Kong (Y.W.), by Hong Kong Research Grant Council grants HKU 778007(Y.W.) and HKU 7645/06M (A.X), by the U.S. National Institutes of Health grant HL-51586 (L.C), and by the Area of Excellent Scheme (AoE/P-10-01) established under the University Grants Committee of the Hong Kong Special Administrative Region.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorZhou, Men_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorTam, PKHen_HK
dc.contributor.authorLam, KSLen_HK
dc.contributor.authorChan, Len_HK
dc.contributor.authorHoo, RLCen_HK
dc.contributor.authorLiu, Jen_HK
dc.contributor.authorChow, KHMen_HK
dc.contributor.authorWang, Yen_HK
dc.date.accessioned2010-09-17T10:19:32Z-
dc.date.available2010-09-17T10:19:32Z-
dc.date.issued2008en_HK
dc.identifier.citationHepatology, 2008, v. 48 n. 4, p. 1087-1096en_HK
dc.identifier.issn0270-9139en_HK
dc.identifier.urihttp://hdl.handle.net/10722/91446-
dc.description.abstractAdiponectin is an adipocyte-derived hormone with a wide range of beneficial effects on obesity-related medical complications. Numerous epidemiological investigations in diverse ethnic groups have identified a lower adiponectin level as an independent risk factor for nonalcoholic fatty liver diseases and liver dysfunctions. Animal studies have demonstrated that replenishment of adiponectin protects against various forms of hepatic injuries, suggesting it to be a potential drug candidate for the treatment of liver diseases. This study was designed to investigate the cellular and molecular mechanisms underlying the hepatoprotective effects of adiponectin. Our results demonstrated that in adiponectin knockout (ADN-KO) mice, there was a preexisting condition of hepatic steatosis and mitochondrial dysfunction that might contribute to the increased vulnerabilities of these mice to secondary liver injuries induced by obesity and other conditions. Adenovirus-mediated replenishment of adiponectin depleted lipid accumulation, restored the oxidative activities of mitochondrial respiratory chain (MRC) complexes, and prevented the accumulation of lipid peroxidation products in ADN-KO mice but had no obvious effects on mitochondrial biogenesis. The gene and protein levels of uncoupling protein 2 (UCP2), a mitochondrial membrane transporter, were decreased in ADN-KO mice and could be significantly up-regulated by adiponectin treatment. Moreover, the effects of adiponectin on mitochondrial activities and on protection against endotoxin-induced liver injuries were significantly attenuated in UCP2 knockout mice. Conclusion: These results suggest that the hepatoprotective properties of adiponectin are mediated at least in part by an enhancement of the activities of MRC complexes through a mechanism involving UCP2. Copyright © 2008 by the American Association for the Study of Liver Diseases.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/en_HK
dc.relation.ispartofHepatologyen_HK
dc.rightsHepatology. Copyright © John Wiley & Sons, Inc.-
dc.titleMitochondrial dysfunction contributes to the increased vulnerabilities of adiponectin knockout mice to liver injuryen_HK
dc.typeArticleen_HK
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_HK
dc.identifier.emailTam, PKH: paultam@hkucc.hku.hken_HK
dc.identifier.emailLam, KSL: ksllam@hku.hken_HK
dc.identifier.emailHoo, RLC: rubyhoo@hkucc.hku.hken_HK
dc.identifier.emailWang, Y: yuwanghk@hku.hken_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.identifier.authorityTam, PKH=rp00060en_HK
dc.identifier.authorityLam, KSL=rp00343en_HK
dc.identifier.authorityHoo, RLC=rp01334en_HK
dc.identifier.authorityWang, Y=rp00239en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1002/hep.22444en_HK
dc.identifier.pmid18698578-
dc.identifier.pmcidPMC2597507-
dc.identifier.scopuseid_2-s2.0-54449085766en_HK
dc.identifier.hkuros157394-
dc.identifier.hkuros226336-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-54449085766&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume48en_HK
dc.identifier.issue4en_HK
dc.identifier.spage1087en_HK
dc.identifier.epage1096en_HK
dc.identifier.eissn1527-3350-
dc.identifier.isiWOS:000259757000010-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectHypoxia inducible factor 1α as a mediator of obesity-induced chronic inflammation, aberrant production of adipokines, and insulin resistance-
dc.identifier.scopusauthoridZhou, M=14629760500en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridTam, PKH=7202539421en_HK
dc.identifier.scopusauthoridLam, KSL=8082870600en_HK
dc.identifier.scopusauthoridChan, L=24439401800en_HK
dc.identifier.scopusauthoridHoo, RLC=6602369766en_HK
dc.identifier.scopusauthoridLiu, J=36066808300en_HK
dc.identifier.scopusauthoridChow, KHM=26430472800en_HK
dc.identifier.scopusauthoridWang, Y=34973733700en_HK

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