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Article: Rosiglitazone promotes fatty acyl CoA accumulation and excessive glycogen storage in livers of mice without adiponectin

TitleRosiglitazone promotes fatty acyl CoA accumulation and excessive glycogen storage in livers of mice without adiponectin
Authors
KeywordsAdiponectin
Liver injury
Mitochondria
Rosiglitazone
Uncoupling protein 2
Issue Date2010
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep
Citation
Journal Of Hepatology, 2010, v. 53 n. 6, p. 1108-1116 How to Cite?
AbstractBackground & Aims: The beneficial effects of rosiglitazone on non-alcoholic fatty liver disease (NAFLD) have been reported. Rosiglitazone treatment stimulates the production of adiponectin, an insulin-sensitizing adipokine with hepatoprotective functions. The present study aims to investigate the hepatic actions of rosiglitazone in mice without adiponectin. Methods: NAFLD was induced in wild type and adiponectin knockout (AKO) mice by high-fat diet feeding. After rosiglitazone treatment, mice were subjected to evaluations on systemic insulin sensitivity, lipid profiles, hepatic steatosis, and inflammation, as well as the expression and activity of key molecules involved in energy metabolism and mitochondrial functions. Results: Rosiglitazone treatment prevented hepatic inflammation and reduced the expression of pro-inflammatory cytokines in livers of wild type mice. In contrast, in livers of AKO mice, the same treatment induced severe hepatomegaly and microvesicular hepatosteatosis, and caused abnormal accumulation of fatty acyl CoA, glycogen, and their intermediate metabolites. Compared to wild type littermates, the anti-inflammatory and the mitochondria-stimulatory activity of rosiglitazone were largely attenuated in AKO mice. Replenishment with either adiponectin or uncoupling protein 2 (UCP2) significantly reduced fatty acyl CoA accumulation and increased mitochondrial activities in livers of rosiglitazone-treated AKO mice. In addition, adiponectin, but not UCP2, promoted the activation of glycogen synthase kinase 3beta (GSK3beta), a key molecule involved in regulating glycogen homeostasis. Conclusions: Rosiglitazone elicits its protective functions against NAFLD largely through the induction of adiponectin, which prevents mitochondria stresses by promoting GSK3beta activation and UCP2 upregulation, two pathways coordinating the glucose and lipid metabolism in liver. © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/134711
ISSN
2015 Impact Factor: 10.59
2015 SCImago Journal Rankings: 4.570
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of Hong Kong777908M
National Basic Research Program of China2010CB945500 2011CB504004
University Grants Committee HKSARAoE/P-10-01
US National Institutes of HealthHL-51586
Funding Information:

Financial support This work is supported in part by Research Grants Council of Hong Kong (Project No 777908M) the National Basic Research Program of China (2010CB945500 2011CB504004) and the Area of Excellent Scheme (AoE/P-10-01) established under the University Grants Committee HKSAR Adiponectin knockout mice were kindly provided by Dr Lawrence Chan at Baylor College of Medicine who generated these mice with the support of the US National Institutes of Health Grant HL-51586

References

 

DC FieldValueLanguage
dc.contributor.authorZhou, Men_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorLam, KSLen_HK
dc.contributor.authorTam, PKHen_HK
dc.contributor.authorChe, CMen_HK
dc.contributor.authorChan, Len_HK
dc.contributor.authorLee, IKen_HK
dc.contributor.authorWu, Den_HK
dc.contributor.authorWang, Yen_HK
dc.date.accessioned2011-07-07T05:00:48Z-
dc.date.available2011-07-07T05:00:48Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal Of Hepatology, 2010, v. 53 n. 6, p. 1108-1116en_HK
dc.identifier.issn0168-8278en_HK
dc.identifier.urihttp://hdl.handle.net/10722/134711-
dc.description.abstractBackground & Aims: The beneficial effects of rosiglitazone on non-alcoholic fatty liver disease (NAFLD) have been reported. Rosiglitazone treatment stimulates the production of adiponectin, an insulin-sensitizing adipokine with hepatoprotective functions. The present study aims to investigate the hepatic actions of rosiglitazone in mice without adiponectin. Methods: NAFLD was induced in wild type and adiponectin knockout (AKO) mice by high-fat diet feeding. After rosiglitazone treatment, mice were subjected to evaluations on systemic insulin sensitivity, lipid profiles, hepatic steatosis, and inflammation, as well as the expression and activity of key molecules involved in energy metabolism and mitochondrial functions. Results: Rosiglitazone treatment prevented hepatic inflammation and reduced the expression of pro-inflammatory cytokines in livers of wild type mice. In contrast, in livers of AKO mice, the same treatment induced severe hepatomegaly and microvesicular hepatosteatosis, and caused abnormal accumulation of fatty acyl CoA, glycogen, and their intermediate metabolites. Compared to wild type littermates, the anti-inflammatory and the mitochondria-stimulatory activity of rosiglitazone were largely attenuated in AKO mice. Replenishment with either adiponectin or uncoupling protein 2 (UCP2) significantly reduced fatty acyl CoA accumulation and increased mitochondrial activities in livers of rosiglitazone-treated AKO mice. In addition, adiponectin, but not UCP2, promoted the activation of glycogen synthase kinase 3beta (GSK3beta), a key molecule involved in regulating glycogen homeostasis. Conclusions: Rosiglitazone elicits its protective functions against NAFLD largely through the induction of adiponectin, which prevents mitochondria stresses by promoting GSK3beta activation and UCP2 upregulation, two pathways coordinating the glucose and lipid metabolism in liver. © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.en_HK
dc.languageeng-
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhepen_HK
dc.relation.ispartofJournal of Hepatologyen_HK
dc.subjectAdiponectinen_HK
dc.subjectLiver injuryen_HK
dc.subjectMitochondriaen_HK
dc.subjectRosiglitazoneen_HK
dc.subjectUncoupling protein 2en_HK
dc.subject.meshAcyl Coenzyme A - metabolism-
dc.subject.meshLiver - drug effects - injuries - metabolism-
dc.subject.meshLiver Glycogen - metabolism-
dc.subject.meshThiazolidinediones - toxicity-
dc.subject.meshLiver Glycogen - metabolism-
dc.titleRosiglitazone promotes fatty acyl CoA accumulation and excessive glycogen storage in livers of mice without adiponectinen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0168-8278&volume=53&issue=6&spage=1108&epage=1116&date=2010&atitle=Rosiglitazone+promotes+fatty+acyl+CoA+accumulation+and+excessive+glycogen+storage+in+livers+of+mice+without+adiponectin-
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_HK
dc.identifier.emailLam, KSL: ksllam@hku.hken_HK
dc.identifier.emailTam, PKH: paultam@hkucc.hku.hken_HK
dc.identifier.emailChe, CM: cmche@hku.hken_HK
dc.identifier.emailWang, Y: yuwanghk@hku.hken_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.identifier.authorityLam, KSL=rp00343en_HK
dc.identifier.authorityTam, PKH=rp00060en_HK
dc.identifier.authorityChe, CM=rp00670en_HK
dc.identifier.authorityWang, Y=rp00239en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.jhep.2010.05.034en_HK
dc.identifier.pmid20828853en_HK
dc.identifier.scopuseid_2-s2.0-78049452814en_HK
dc.identifier.hkuros183845-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78049452814&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume53en_HK
dc.identifier.issue6en_HK
dc.identifier.spage1108en_HK
dc.identifier.epage1116en_HK
dc.identifier.isiWOS:000284918000020-
dc.publisher.placeNetherlandsen_HK
dc.identifier.scopusauthoridZhou, M=14629760500en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridLam, KSL=8082870600en_HK
dc.identifier.scopusauthoridTam, PKH=7202539421en_HK
dc.identifier.scopusauthoridChe, CM=7102442791en_HK
dc.identifier.scopusauthoridChan, L=24439401800en_HK
dc.identifier.scopusauthoridLee, IK=36071537600en_HK
dc.identifier.scopusauthoridWu, D=7404297751en_HK
dc.identifier.scopusauthoridWang, Y=34973733700en_HK
dc.identifier.citeulike7590934-

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