title: Hyperuricemia as a mediator of the proinflammatory endocrine imbalance in the adipose tissue in a murine model of the metabolic syndrome.
abstract: OBJECTIVE
  Hyperuricemia is strongly associated with obesity and metabolic syndrome and can predict visceral obesity and insulin resistance. Previously, we showed that soluble uric acid directly stimulated the redox-dependent proinflammatory signaling in adipocytes. In this study we demonstrate the role of hyperuricemia in the production of key adipokines.
  
  
  METHODS
  We used mouse 3T3-L1 adipocytes, human primary adipocytes, and a mouse model of metabolic syndrome and hyperuricemia.
  
  
  RESULTS
  Uric acid induced in vitro an increase in the production (mRNA and secreted protein) of monocyte chemotactic protein-1 (MCP-1), an adipokine playing an essential role in inducing the proinflammatory state in adipocytes in obesity. In addition, uric acid caused a decrease in the production of adiponectin, an adipocyte-specific insulin sensitizer and anti-inflammatory agent. Uric acid-induced increase in MCP-1 production was blocked by scavenging superoxide or by inhibiting NADPH oxidase and by stimulating peroxisome-proliferator-activated receptor-γ with rosiglitazone. Downregulation of the adiponectin production was prevented by rosiglitazone but not by antioxidants. In obese mice with metabolic syndrome, we observed hyperuricemia. Lowering uric acid in these mice by inhibiting xanthine oxidoreductase with allopurinol could improve the proinflammatory endocrine imbalance in the adipose tissue by reducing production of MCP-1 and increasing production of adiponectin. In addition, lowering uric acid in obese mice decreased macrophage infiltration in the adipose tissue and reduced insulin resistance.
  
  
  CONCLUSIONS
  Hyperuricemia might be partially responsible for the proinflammatory endocrine imbalance in the adipose tissue, which is an underlying mechanism of the low-grade inflammation and insulin resistance in subjects with the metabolic syndrome.
authors.affiliation: Department of Medicine, University of Florida, Gainesville, Florida, USA.
authors.forename: William
authors.initials: W
authors.lastname: Baldwin
authors.forename: Steven
authors.initials: S
authors.lastname: McRae
authors.forename: George
authors.initials: G
authors.lastname: Marek
authors.forename: David
authors.initials: D
authors.lastname: Wymer
authors.forename: Varinderpal
authors.initials: V
authors.lastname: Pannu
authors.forename: Chris
authors.initials: C
authors.lastname: Baylis
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
authors.forename: Yuri Y
authors.initials: YY
authors.lastname: Sautin
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000097:blood; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000378:metabolism*; D007150:Immunohistochemistry; D024821:Metabolic Syndrome / Q000097:blood / Q000378:metabolism*; D051379:Mice; D008820:Mice, Obese; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013858:Thiobarbiturates / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism
chemical_list: D052242:Adiponectin; D018932:Chemokine CCL2; D013858:Thiobarbiturates; D014527:Uric Acid; C029684:thiobarbituric acid