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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid, Acute-Phase Proteins, Adiponectin, Adipose Tissue, Animals, Blood Glucose, Crosses, Genetic, Female, Glucose, Insulin, Insulin Resistance, Lipid Peroxidation, Lipids, Lipocalin-2, Lipocalins, Liver, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle, Skeletal, Obesity, Oncogene Proteins, Receptors, Leptin, Tumor Necrosis Factor-alpha.
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Does lipocalin-2 deficiency attenuate insulin resistance associated with aging and obesity? Context: 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. 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-alpha (TNF-alpha), 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-alpha production in fat tissues. Cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate (CDC), an arachidonate lipoxygenase inhibitor, prevents TNF-alpha expression induced by lipocalin-2. Moreover, treatment with TNF-alpha neutralization antibody or CDC significantly attenuated the differences of insulin sensitivity between wild-type and Lcn2-KO mice.
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Lipocalin-2 deficiency protects mice from developing aging- and obesity-induced insulin resistance largely by modulating 12-lipoxygenase and TNF-alpha levels in adipose tissue. Final Decision: yes