title: Fetuin-A induces cytokine expression and suppresses adiponectin production.
abstract: BACKGROUND
  The secreted liver protein fetuin-A (AHSG) is up-regulated in hepatic steatosis and the metabolic syndrome. These states are strongly associated with low-grade inflammation and hypoadiponectinemia. We, therefore, hypothesized that fetuin-A may play a role in the regulation of cytokine expression, the modulation of adipose tissue expression and plasma concentration of the insulin-sensitizing and atheroprotective adipokine adiponectin.
  
  
  RESULTS
  Human monocytic THP1 cells and human in vitro differenttiated adipocytes as well as C57BL/6 mice were treated with fetuin-A. mRNA expression of the genes encoding inflammatory cytokines and the adipokine adiponectin (ADIPOQ) was assessed by real-time RT-PCR. In 122 subjects, plasma levels of fetuin-A, adiponectin and, in a subgroup, the multimeric forms of adiponectin were determined. Fetuin-A treatment induced TNF and IL1B mRNA expression in THP1 cells (p<0.05). Treatment of mice with fetuin-A, analogously, resulted in a marked increase in adipose tissue Tnf mRNA as well as Il6 expression (27- and 174-fold, respectively). These effects were accompanied by a decrease in adipose tissue Adipoq mRNA expression and lower circulating adiponectin levels (p<0.05, both). Furthermore, fetuin-A repressed ADIPOQ mRNA expression of human in vitro differentiated adipocytes (p<0.02) and induced inflammatory cytokine expression. In humans in plasma, fetuin-A correlated positively with high-sensitivity C-reactive protein, a marker of subclinical inflammation (r = 0.26, p = 0.01), and negatively with total- (r = -0.28, p = 0.02) and, particularly, high molecular weight adiponectin (r = -0.36, p = 0.01).
  
  
  CONCLUSIONS
  We provide novel evidence that the secreted liver protein fetuin-A induces low-grade inflammation and represses adiponectin production in animals and in humans. These data suggest an important role of fatty liver in the pathophysiology of insulin resistance and atherosclerosis.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Nephrology, Vascular Disease and Clinical Chemistry, University of Tübingen, Tübingen, Germany.
authors.forename: Anita M
authors.initials: AM
authors.lastname: Hennige
authors.forename: Harald
authors.initials: H
authors.lastname: Staiger
authors.forename: Corinna
authors.initials: C
authors.lastname: Wicke
authors.forename: Fausto
authors.initials: F
authors.lastname: Machicao
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Häring
authors.forename: Norbert
authors.initials: N
authors.lastname: Stefan
mesh_terms: D052242:Adiponectin / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000509:alpha-Fetoproteins / Q000502:physiology*
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D016207:Cytokines; D012333:RNA, Messenger; D000509:alpha-Fetoproteins