title: Proinflammatory and antiinflammatory attributes of fetuin-a: a novel hepatokine modulating cardiovascular and glycemic outcomes in metabolic syndrome.
abstract: 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.
  
  
  CONCLUSIONS
  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-β, 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.
authors.affiliation: Department of Endocrinology & Metabolism, Institute of Post-Graduate Medical Education & Research (IPGMER) and Seth Sukhlal Karnani Memorial (SSKM) Hospital, Calcutta, India.
authors.forename: Satinath
authors.initials: S
authors.lastname: Mukhopadhyay
authors.affiliation: Department of Biochemistry, IPGMER & SSKM Hospital, Dr. B C Roy Post-Graduate Institute of Basic Medical Education and Research, Calcutta, India.
authors.forename: Samim A
authors.initials: SA
authors.lastname: Mondal
authors.affiliation: Department of Endocrinology & Metabolism, Institute of Post-Graduate Medical Education & Research (IPGMER) and Seth Sukhlal Karnani Memorial (SSKM) Hospital, Calcutta, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Department of Endocrinology, Post-Graduate Institute of Medical Education & Research & Dr. Ram Manohar Lohia Hospital, New Delhi, India.
authors.forename: Deep
authors.initials: D
authors.lastname: Dutta