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Adipokine Orosomucoid Restores Adipose Tissue Inflammation and Energy Homeostasis in Obesity

Orosomucoid (ORM), also called α‐1 acid glycoprotein, is an abundant plasma protein that is an immunomodulator induced by stressful conditions such as infections. We observed that ORM is induced selectively in the adipose tissue of obese mice and highly expressed in adipocyte fraction. Adipose ORM levels were elevated by metabolic signals including insulin, high glucose, and free fatty acid, as well as proinflammatory cytokine such as Tumor Necrosis Factor (TNF)α. ORM suppressed proinflammatory gene expression in adipocytes and suppressed interaction between adipocyte and macrophage. In addition, ORM suppressed TNFα‐induced Nuclear Factor Kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) and Mitogen‐Activated Protein Kinase(MAPK). Concomitantly, ORM relieved hyperglycemia‐induced insulin resistance as well as TNFα‐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.