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Article: Selective inactivation of c-Jun NH 2-terminal kinase in adipose tissue protects against diet-induced obesity and improves insulin sensitivity in both liver and skeletal muscle in mice

TitleSelective inactivation of c-Jun NH 2-terminal kinase in adipose tissue protects against diet-induced obesity and improves insulin sensitivity in both liver and skeletal muscle in mice
Authors
Issue Date2011
PublisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/
Citation
Diabetes, 2011, v. 60 n. 2, p. 486-495 How to Cite?
AbstractOBJECTIVE - Obesity is associated with increased activation of the c-Jun NH 2-terminal kinase (JNK) in several metabolic organs, including adipose tissue, liver, and skeletal muscle. In this study, we aimed to define the role of JNK activation in adipose tissue in the development of obesity-related insulin resistance. RESEARCH DESIGN AND METHODS - Transgenic mice with adipose tissue-specific overexpression of dominant-negative JNK (ap2-dn-JNK) under the transcriptional control of the aP2 gene promoter were generated and subjected to metabolic characterization together with the wild-type littermates. RESULTS - On a high-fat diet (HFD), the ap2-dn-JNK mice displayed a marked suppression of both JNK1 and JNK2 activation in their adipose tissue, accompanied by a marked reduction in weight gain, fat mass, and size of the adipocytes. The transgenic mice were resistant to the deleterious impact of an HFD on systemic insulin sensitivity, glucose tolerance, and hepatic steatosis. Reduced hepatic gluconeogenesis was evident in in vivo and ex vivo studies and showed greater insulin-induced glucose uptake in skeletal muscles. These changes were accompanied by reduced macrophage infiltration in adipose tissue, decreased production of proinflammatory adipokines, and increased expression of adiponectin. Indirect calorimetry analysis showed that the transgenic mice had significant increases in oxygen consumption and reductions in respiration exchange rates compared with their wild-type littermates. CONCLUSIONS - Selective suppression of JNK activation in adipose tissue alone is sufficient to counteract HFD-induced obesity and its associated metabolic dysregulations, in part through an increase in energy expenditure and a decrease in systemic inflammation. © 2011 by the American Diabetes Association.
Persistent Identifierhttp://hdl.handle.net/10722/142380
ISSN
2015 Impact Factor: 8.784
2015 SCImago Journal Rankings: 5.185
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grant Council767208M
Collaborative Research FundHKU 2/07C
National Basic Research Program of China2011CB504004
Funding Information:

This work was supported by a general research fund grant from the Hong Kong Research Grant Council (767208M; to K.S.L.L.) and the Collaborative Research Fund (HKU 2/07C) and the National Basic Research Program of China (2011CB504004). No potential conflicts of interest relevant to this article were reported.

References
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DC FieldValueLanguage
dc.contributor.authorZhang, Xen_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorChung, SKen_HK
dc.contributor.authorCresser, JHBen_HK
dc.contributor.authorSweeney, Gen_HK
dc.contributor.authorWong, RLCen_HK
dc.contributor.authorLin, Aen_HK
dc.contributor.authorLam, KSLen_HK
dc.date.accessioned2011-10-28T02:44:43Z-
dc.date.available2011-10-28T02:44:43Z-
dc.date.issued2011en_HK
dc.identifier.citationDiabetes, 2011, v. 60 n. 2, p. 486-495en_HK
dc.identifier.issn0012-1797en_HK
dc.identifier.urihttp://hdl.handle.net/10722/142380-
dc.description.abstractOBJECTIVE - Obesity is associated with increased activation of the c-Jun NH 2-terminal kinase (JNK) in several metabolic organs, including adipose tissue, liver, and skeletal muscle. In this study, we aimed to define the role of JNK activation in adipose tissue in the development of obesity-related insulin resistance. RESEARCH DESIGN AND METHODS - Transgenic mice with adipose tissue-specific overexpression of dominant-negative JNK (ap2-dn-JNK) under the transcriptional control of the aP2 gene promoter were generated and subjected to metabolic characterization together with the wild-type littermates. RESULTS - On a high-fat diet (HFD), the ap2-dn-JNK mice displayed a marked suppression of both JNK1 and JNK2 activation in their adipose tissue, accompanied by a marked reduction in weight gain, fat mass, and size of the adipocytes. The transgenic mice were resistant to the deleterious impact of an HFD on systemic insulin sensitivity, glucose tolerance, and hepatic steatosis. Reduced hepatic gluconeogenesis was evident in in vivo and ex vivo studies and showed greater insulin-induced glucose uptake in skeletal muscles. These changes were accompanied by reduced macrophage infiltration in adipose tissue, decreased production of proinflammatory adipokines, and increased expression of adiponectin. Indirect calorimetry analysis showed that the transgenic mice had significant increases in oxygen consumption and reductions in respiration exchange rates compared with their wild-type littermates. CONCLUSIONS - Selective suppression of JNK activation in adipose tissue alone is sufficient to counteract HFD-induced obesity and its associated metabolic dysregulations, in part through an increase in energy expenditure and a decrease in systemic inflammation. © 2011 by the American Diabetes Association.en_HK
dc.languageengen_US
dc.publisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/en_HK
dc.relation.ispartofDiabetesen_HK
dc.subject.meshAdipose Tissue - metabolism-
dc.subject.meshInsulin - metabolism-
dc.subject.meshJNK Mitogen-Activated Protein Kinases - genetics - metabolism-
dc.subject.meshLiver - metabolism-
dc.subject.meshMuscle, Skeletal - metabolism-
dc.titleSelective inactivation of c-Jun NH 2-terminal kinase in adipose tissue protects against diet-induced obesity and improves insulin sensitivity in both liver and skeletal muscle in miceen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0012-1797&volume=60&issue=2&spage=486&epage=495&date=2011&atitle=Selective+inactivation+of+c-Jun+NH2-terminal+kinase+in+adipose+tissue+protects+against+diet-induced+obesity+and+improves+insulin+sensitivity+in+both+liver+and+skeletal+muscle+in+miceen_US
dc.identifier.emailXu, A:amxu@hkucc.hku.hken_HK
dc.identifier.emailChung, SK:skchung@hkucc.hku.hken_HK
dc.identifier.emailLam, KSL:ksllam@hku.hken_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.identifier.authorityChung, SK=rp00381en_HK
dc.identifier.authorityLam, KSL=rp00343en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.2337/db10-0650en_HK
dc.identifier.pmid21270260en_HK
dc.identifier.pmcidPMC3028348-
dc.identifier.scopuseid_2-s2.0-79551600855en_HK
dc.identifier.hkuros184651en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79551600855&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume60en_HK
dc.identifier.issue2en_HK
dc.identifier.spage486en_HK
dc.identifier.epage495en_HK
dc.identifier.eissn1939-327X-
dc.identifier.isiWOS:000287172100017-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectVascular dysfunction in obesity and diabetes: from risk prediction to therapeutic intervention-
dc.identifier.scopusauthoridZhang, X=37052942100en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridChung, SK=7404292976en_HK
dc.identifier.scopusauthoridCresser, JHB=36496575600en_HK
dc.identifier.scopusauthoridSweeney, G=7102852659en_HK
dc.identifier.scopusauthoridWong, RLC=26434054000en_HK
dc.identifier.scopusauthoridLin, A=7402061900en_HK
dc.identifier.scopusauthoridLam, KSL=8082870600en_HK
dc.identifier.citeulike8696700-

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