Adipocytokine orosomucoid integrates inflammatory and metabolic signals to preserve energy homeostasis by resolving immoderate inflammation.

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.

• Authors: 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
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 285 Issue 29 Pg. 22174-85 (Jul 16 2010) ISSN: 1083-351X [Electronic] United States
• PMID: 20442402 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adipokines
• CCAAT-Enhancer-Binding Proteins
• Dietary Fats
• Insulin
• NF-kappa B
• Orosomucoid
• Sterol Regulatory Element Binding Protein 1
• Tumor Necrosis Factor-alpha
• Mitogen-Activated Protein Kinases

Topics

• Adipocytes (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)