Back to Search
Start Over
Adipocytokine Orosomucoid Integrates Inflammatory and Metabolic Signals to Preserve Energy Homeostasis by Resolving Immoderate Inflammation
- Source :
- Journal of Biological Chemistry. 285:22174-22185
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
Abstract
- 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.
- Subjects :
- medicine.medical_specialty
medicine.medical_treatment
Mice, Obese
Adipose tissue
Inflammation
Biology
Biochemistry
Cell Line
Diabetes Mellitus, Experimental
Proinflammatory cytokine
Mice
chemistry.chemical_compound
Insulin resistance
Adipokines
Cell Movement
Adipocyte
Internal medicine
Adipocytes
medicine
Animals
Homeostasis
Humans
Insulin
Lipolysis
Molecular Biology
Tumor Necrosis Factor-alpha
Macrophages
NF-kappa B
Feeding Behavior
Orosomucoid
Cell Biology
medicine.disease
Dietary Fats
Metabolism
Endocrinology
Adipose Tissue
chemistry
CCAAT-Enhancer-Binding Proteins
Tumor necrosis factor alpha
Insulin Resistance
Mitogen-Activated Protein Kinases
medicine.symptom
Energy Metabolism
Sterol Regulatory Element Binding Protein 1
Signal Transduction
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 285
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....f8baf5d3bd43af5f9a1fd0ee4bd5e9a5