title: Superantigen activates the gp130 receptor on adipocytes resulting in altered adipocyte metabolism.
abstract: OBJECTIVE
  The bacteria Staphylococcus aureus is part of the normal bacterial flora and produces a repertoire of enterotoxins which can cause food poisoning and toxic shock and might contribute to the pathogenesis of inflammatory diseases. These enterotoxins directly cross-link the T cell receptor with MHC class II, activating large amounts of T cells and are therefore called superantigens. It was recently discovered that the superantigen SEA binds to the cytokine receptor gp130. As obesity and type 2 diabetes are highly associated with inflammation of the adipose tissue and gp130 has been shown to play an important role in adipocytes, we wanted to investigate the effect of SEA on adipocyte signaling and function.
  
  
  METHODS
  Binding of SEA to gp130 was examined using surface plasmon resonance in a cell free system. Effects of SEA on adipocyte signaling, insulin sensitivity and function were studied using western blotting and biological assays for lipolysis, lipogenesis and glucose uptake.
  
  
  RESULTS
  We demonstrate that SEA binds to gp130 with a medium affinity. Furthermore, SEA induces phosphorylation of a key downstream target, STAT3, in adipocytes. SEA also inhibits insulin-induced activation of PKB and PKB downstream signaling which was associated with reduced basal and insulin induced glucose uptake, reduced lipogenesis as well as reduced ability of insulin to inhibit lipolysis.
  
  
  CONCLUSIONS
  SEA inhibits insulin signaling as well as insulin biological responses in adipocytes supporting that bacterial infection might contribute to the development of insulin resistance and type 2 diabetes.
authors.affiliation: Department of Experimental Medical Science, Lund University, BMC, 221 84 Lund, Sweden. Electronic address: elin.banke@med.lu.se.
authors.forename: Elin
authors.initials: E
authors.lastname: Banke
authors.affiliation: Department of Experimental Medical Science, Lund University, BMC, 221 84 Lund, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Rödström
authors.affiliation: Department of Surgery, Skåne University Hospital & Lund University, 221 85 Lund, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Ekelund
authors.affiliation: Department of Experimental Medical Science, Lund University, BMC, 221 84 Lund, Sweden.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Dalla-Riva
authors.affiliation: Department of Experimental Medical Science, Lund University, BMC, 221 84 Lund, Sweden.
authors.forename: Jens O
authors.initials: JO
authors.lastname: Lagerstedt
authors.affiliation: Pure and Applied Biochemistry, Center for Chemistry and Chemical Engineering, Lund University, 221 00 Lund, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.affiliation: Department of Experimental Medical Science, Lund University, BMC, 221 84 Lund, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Degerman
authors.affiliation: Department of Experimental Medical Science, Lund University, BMC, 221 84 Lund, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Lindkvist-Petersson
authors.affiliation: Department of Laboratory Medicine, Division of Medicinal Microbiology, Lund University, 223 62 Lund, Sweden; Department of Clinical Microbiology, University and Regional Laboratories in Region Skåne, 221 85 Lund, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Nilson
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D001424:Bacterial Infections / Q000150:complications / Q000378:metabolism* / Q000382:microbiology; D001681:Biological Assay; D015153:Blotting, Western; D050822:Cytokine Receptor gp130 / Q000187:drug effects* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000382:microbiology*; D004591:Electrophoresis, Polyacrylamide Gel; D004768:Enterotoxins; D048168:Escherichia coli K12; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D050356:Lipid Metabolism; D050155:Lipogenesis; D008066:Lipolysis; D010766:Phosphorylation / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018089:Superantigens / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D004268:DNA-Binding Proteins; D004768:Enterotoxins; D007328:Insulin; D050796:STAT3 Transcription Factor; D018089:Superantigens; D050822:Cytokine Receptor gp130; C026066:enterotoxin A, Staphylococcal; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein; D005947:Glucose
keywords: Glucose- and lipid metabolism; Insulin sensitivity; SEA