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Article: Lipocalin-2 deficiency attenuates insulin resistance associated with aging and obesity

TitleLipocalin-2 deficiency attenuates insulin resistance associated with aging and obesity
Authors
Issue Date2010
PublisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/
Citation
Diabetes, 2010, v. 59 n. 4, p. 872-882 How to Cite?
AbstractOBJECTIVE - The proinflammatory cytokines/adipokines produced from adipose tissue act in an autocrine and/or endocrine manner to perpetuate local inflammation and to induce peripheral insulin resistance. The present study investigates whether lipocalin-2 deficiency or replenishment with this adipokine has any impact on systemic insulin sensitivity and the underlying mechanisms. METHODS AND RESULTS - Under conditions of aging or dietary-/genetic-induced obesity, lipocalin-2 knockout (Lcn2-KO) mice show significantly decreased fasting glucose and insulin levels and improved insulin sensitivity compared with their wild-type littermates. Despite enlarged fat mass, inflammation and the accumulation of lipid peroxidation products are significantly attenuated in the adipose tissues of Lcn2-KO mice. Adipose fatty acid composition of these mice varies significantly from that in wild-type animals. The amounts of arachidonic acid (C20:4 n6) are elevated by aging and obesity and are paradoxically further increased in adipose tissue, but not skeletal muscle and liver of Lcn2-KO mice. On the other hand, the expression and activity of 12-lipoxygenase, an enzyme responsible for metabolizing arachidonic acid, and the production of tumor necrosis factor-α (TNF-α), a critical insulin resistance-inducing factor, are largely inhibited by lipocalin-2 deficiency. Lipocalin-2 stimulates the expression and activity of 12-lipoxygenase and TNF-α production in fat tissues. Cinnamyl-3,4- dihydroxy-α-cyanocinnamate (CDC), an arachidonate lipoxygenase inhibitor, prevents TNF-α expression induced by lipocalin-2. Moreover, treatment with TNF-α neutralization antibody or CDC significantly attenuated the differences of insulin sensitivity between wild-type and Lcn2-KO mice. CONCLUSIONS - Lipocalin-2 deficiency protects mice from developing aging- and obesity-induced insulin resistance largely by modulating 12-lipoxygenase and TNF-α levels in adipose tissue. © 2010 by the American Diabetes Association.
Persistent Identifierhttp://hdl.handle.net/10722/125254
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 CouncilHKU 778007
HKU 7645/06M
Collaborative Research FundHKU 2/07C
University Grants Committee, HKSARAoE/P-10-01
Funding Information:

This work was supported by grants from Hong Kong Research Grant Council HKU 778007 (Y.W.) and HKU 7645/06M (A.X.), the Collaborative Research Fund (HKU 2/07C), and the Area of Excellent Scheme (AoE/P-10-01) established under the University Grants Committee, HKSAR.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorLaw, IKMen_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorLam, KSLen_HK
dc.contributor.authorBerger, Ten_HK
dc.contributor.authorMak, TWen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.contributor.authorLiu, JTCen_HK
dc.contributor.authorSweeney, Gen_HK
dc.contributor.authorZhou, Men_HK
dc.contributor.authorYang, Ben_HK
dc.contributor.authorWang, Yen_HK
dc.date.accessioned2010-10-31T11:20:15Z-
dc.date.available2010-10-31T11:20:15Z-
dc.date.issued2010en_HK
dc.identifier.citationDiabetes, 2010, v. 59 n. 4, p. 872-882en_HK
dc.identifier.issn0012-1797en_HK
dc.identifier.urihttp://hdl.handle.net/10722/125254-
dc.description.abstractOBJECTIVE - The proinflammatory cytokines/adipokines produced from adipose tissue act in an autocrine and/or endocrine manner to perpetuate local inflammation and to induce peripheral insulin resistance. The present study investigates whether lipocalin-2 deficiency or replenishment with this adipokine has any impact on systemic insulin sensitivity and the underlying mechanisms. METHODS AND RESULTS - Under conditions of aging or dietary-/genetic-induced obesity, lipocalin-2 knockout (Lcn2-KO) mice show significantly decreased fasting glucose and insulin levels and improved insulin sensitivity compared with their wild-type littermates. Despite enlarged fat mass, inflammation and the accumulation of lipid peroxidation products are significantly attenuated in the adipose tissues of Lcn2-KO mice. Adipose fatty acid composition of these mice varies significantly from that in wild-type animals. The amounts of arachidonic acid (C20:4 n6) are elevated by aging and obesity and are paradoxically further increased in adipose tissue, but not skeletal muscle and liver of Lcn2-KO mice. On the other hand, the expression and activity of 12-lipoxygenase, an enzyme responsible for metabolizing arachidonic acid, and the production of tumor necrosis factor-α (TNF-α), a critical insulin resistance-inducing factor, are largely inhibited by lipocalin-2 deficiency. Lipocalin-2 stimulates the expression and activity of 12-lipoxygenase and TNF-α production in fat tissues. Cinnamyl-3,4- dihydroxy-α-cyanocinnamate (CDC), an arachidonate lipoxygenase inhibitor, prevents TNF-α expression induced by lipocalin-2. Moreover, treatment with TNF-α neutralization antibody or CDC significantly attenuated the differences of insulin sensitivity between wild-type and Lcn2-KO mice. CONCLUSIONS - Lipocalin-2 deficiency protects mice from developing aging- and obesity-induced insulin resistance largely by modulating 12-lipoxygenase and TNF-α levels in adipose tissue. © 2010 by the American Diabetes Association.en_HK
dc.languageengen_HK
dc.publisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/en_HK
dc.relation.ispartofDiabetesen_HK
dc.titleLipocalin-2 deficiency attenuates insulin resistance associated with aging and obesityen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0012-1797&volume=59&spage=872&epage=82&date=2010&atitle=Lipocalin-2+deficiency+attenuates+insulin+resistance+associated+with+ageing+and+obesity.en_HK
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_HK
dc.identifier.emailLam, KSL: ksllam@hku.hken_HK
dc.identifier.emailVanhoutte, PM: vanhoutt@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.authorityVanhoutte, PM=rp00238en_HK
dc.identifier.authorityWang, Y=rp00239en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.2337/db09-1541en_HK
dc.identifier.pmid20068130-
dc.identifier.pmcidPMC2844835-
dc.identifier.scopuseid_2-s2.0-77951193688en_HK
dc.identifier.hkuros173716en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77951193688&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume59en_HK
dc.identifier.issue4en_HK
dc.identifier.spage872en_HK
dc.identifier.epage882en_HK
dc.identifier.eissn1939-327X-
dc.identifier.isiWOS:000276601200013-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectVascular dysfunction in obesity and diabetes: from risk prediction to therapeutic intervention-
dc.relation.projectHypoxia inducible factor 1α as a mediator of obesity-induced chronic inflammation, aberrant production of adipokines, and insulin resistance-
dc.identifier.scopusauthoridLaw, IKM=34872613000en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridLam, KSL=8082870600en_HK
dc.identifier.scopusauthoridBerger, T=12242304800en_HK
dc.identifier.scopusauthoridMak, TW=35269407400en_HK
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_HK
dc.identifier.scopusauthoridLiu, JTC=36081869500en_HK
dc.identifier.scopusauthoridSweeney, G=7102852659en_HK
dc.identifier.scopusauthoridZhou, M=14629760500en_HK
dc.identifier.scopusauthoridYang, B=7404472939en_HK
dc.identifier.scopusauthoridWang, Y=34973733700en_HK

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