Superantigen Activates the gp130 Receptor on Adipocytes Resulting in Altered Adipocyte Metabolism

Metabolism. 2014 Jun;63(6):831-40. doi: 10.1016/j.metabol.2014.03.004. Epub 2014 Mar 11.

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.

Materials/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.

Keywords: Glucose- and lipid metabolism; Insulin sensitivity; SEA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / metabolism*
  • Alcohol Oxidoreductases / metabolism
  • Animals
  • Bacterial Infections / complications
  • Bacterial Infections / metabolism*
  • Bacterial Infections / microbiology
  • Biological Assay
  • Blotting, Western
  • Cytokine Receptor gp130 / drug effects*
  • Cytokine Receptor gp130 / metabolism
  • DNA-Binding Proteins / metabolism
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / microbiology*
  • Electrophoresis, Polyacrylamide Gel
  • Enterotoxins
  • Escherichia coli K12
  • Glucose / metabolism
  • Humans
  • Insulin / metabolism*
  • Insulin Resistance
  • Lipid Metabolism*
  • Lipogenesis
  • Lipolysis
  • Phosphorylation / drug effects
  • STAT3 Transcription Factor / drug effects
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Superantigens / metabolism
  • Superantigens / pharmacology*

Substances

  • DNA-Binding Proteins
  • Enterotoxins
  • Insulin
  • STAT3 Transcription Factor
  • Superantigens
  • Cytokine Receptor gp130
  • enterotoxin A, Staphylococcal
  • Alcohol Oxidoreductases
  • C-terminal binding protein
  • Glucose