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Lipocalin-2 Deficiency Attenuates Insulin Resistance Associated With Aging and Obesity
Authors
A. Xu
B. Yang
+39 more
Catalan
Chakrabarti
Consitt
Cowland
Davis
Fantuzzi
Flower
G. Sweeney
Haan
Hotamisligil
Hotamisligil
Hraba-Renevey
I. K.M. Law
J. T.C. Liu
K. S.L. Lam
Kjeldsen
L gdberg
M. Zhou
Meheus
Mishra
P. M. Vanhoutte
Paolisso
Ruan
Stenger
Stoesz
T. Berger
T. W. Mak
Tataranni
Tilg
Uysal
van Dam
Ventre
Wang
Weisberg
Wellen
Xu
Xu
Xu
Y. Wang
Publication date
1 January 2010
Publisher
American Diabetes Association
Doi
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on
PubMed
Abstract
OBJECTIVE - 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.link_to_OA_fulltex
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Last time updated on 17/02/2019
HKU Scholars Hub
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oai:hub.hku.hk:10722/125254
Last time updated on 01/06/2016