| Adipocytokine orosomucoid integrates inflammatory and metabolic signals to preserve energy homeostasis by resolving immoderate inflammation. | |
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MedLine Citation:
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PMID: 20442402 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Orosomucoid (ORM), also called alpha-1 acid glycoprotein, is an abundant plasma protein that is an immunomodulator induced by stressful conditions such as infections. In this study, we reveal that Orm is induced selectively in the adipose tissue of obese mice to suppress excess inflammation that otherwise disturbs energy homeostasis. Adipose Orm levels were elevated by metabolic signals, including insulin, high glucose, and free fatty acid, as well as by the proinflammatory cytokine tumor necrosis factor-alpha, which is found in increased levels in the adipose tissue of morbid obese subjects. In both adipocytes and macrophages, ORM suppressed proinflammatory gene expression and pathways such as NF-kappaB and mitogen-activated protein kinase signalings and reactive oxygen species generation. Concomitantly, ORM relieved hyperglycemia-induced insulin resistance as well as tumor necrosis factor-alpha-mediated lipolysis in adipocytes. Accordingly, ORM improved glucose and insulin tolerance in obese and diabetic db/db mice. Taken together, our results suggest that ORM integrates inflammatory and metabolic signals to modulate immune responses to protect adipose tissue from excessive inflammation and thereby from metabolic dysfunction. |
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Authors:
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Yun Sok Lee; Jin Woo Choi; Injae Hwang; Joo Won Lee; Jae Ho Lee; A Young Kim; Jin Young Huh; Young Jun Koh; Gou Young Koh; Hee Jung Son; Hiroaki Masuzaki; Kikuko Hotta; Assim A Alfadda; Jae Bum Kim |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-04 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-12 Completed Date: 2010-08-06 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 22174-85 Citation Subset: IM |
Affiliation:
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Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adipocytes
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drug effects,
enzymology,
pathology Adipokines / genetics, metabolism* Adipose Tissue / drug effects, metabolism, pathology Animals CCAAT-Enhancer-Binding Proteins / metabolism Cell Line Cell Movement / drug effects Diabetes Mellitus, Experimental / blood, metabolism Dietary Fats / administration & dosage, pharmacology Energy Metabolism* / drug effects Feeding Behavior / drug effects Homeostasis* / drug effects Humans Inflammation / blood, metabolism*, pathology Insulin / metabolism Insulin Resistance Macrophages / cytology, drug effects, enzymology Mice Mice, Obese Mitogen-Activated Protein Kinases / metabolism NF-kappa B / metabolism Orosomucoid / genetics, metabolism* Signal Transduction* / drug effects Sterol Regulatory Element Binding Protein 1 / metabolism Tumor Necrosis Factor-alpha / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Adipokines; 0/CCAAT-Enhancer-Binding Proteins; 0/Dietary Fats; 0/NF-kappa B; 0/Orosomucoid; 0/Sterol Regulatory Element Binding Protein 1; 0/Tumor Necrosis Factor-alpha; 11061-68-0/Insulin; EC 2.7.11.24/Mitogen-Activated Protein Kinases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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