PROINFLAMMATORY AND ANTIINFLAMMATORY ATTRIBUTES OF FETUIN-A: A NOVEL HEPATOKINE MODULATING CARDIOVASCULAR AND GLYCEMIC OUTCOMES IN METABOLIC SYNDROME

Objective: Fetuin-A is a novel hepatokine. The number of biologic roles attributed to fetuin-A has increased exponentially in the past decade. The objective of this review is to discuss the pathophysiology of fetuin-A action, its proinflammatory and antiinflammatory attributes in different biological systems throughout the body, and pharmacologic interventions that modulate fetuin-A levels. Methods: PubMed, Medline, and Embase search for articles published to July 2014, using the terms alpha-2-hs-glycoprotein [MeSH Terms] OR alpha-2-hs-glycoprotein [All Fields] OR fetuin a [All Fields]. Results: Fetuin-A is the endogenous ligand for Toll-like receptor-4 activation, for lipid-induced insulin resistance. Fetuin-A has inverse interaction with adiponectin. Increased fetuin-A is a risk factor for diabetes and fatty liver disease in normoglycemia and prediabetes. Fetuin-A is a negative acute-phase reactant in sepsis and endotoxemia, promotes wound healing, and is neuroprotective in Alzheimer's disease. Decreased fetuin-A predicts increased disease activity in obstructive lung disease, Crohn's disease, and ulcerative colitis. Both elevated and reduced fetuin-A may be linked with increased cardiovascular events. Conclusion: Fetuin-A is a pleotropic molecule with diverse (sometimes even contradictory) effects in different systems, brought about by interaction with a variety of receptors, including the insulin, transforming growth factor-beta, and a plethora of Toll-like receptors. As a proinflammatory molecule, fetuin-A contributes to insulin resistance and is an important link between liver, adipose tissue, and muscles. Fetuin-A is neuroprotective and plays an important antiinflammatory role in sepsis and autoimmune disorders. Pharmacologic options are limited in modulating serum fetuin-A, but salsalates, curcumin, and vitamin D are promising agents of the future.