Glutamine synthetase desensitizes differentiated adipocytes to proinflammatory stimuli by raising intracellular glutamine levels

FEBS Lett. 2014 Dec 20;588(24):4807-14. doi: 10.1016/j.febslet.2014.11.015. Epub 2014 Nov 20.

Abstract

The role of glutamine synthetase (GS) during adipocyte differentiation is unclear. Here, we assess the impact of GS on the adipocytic response to a proinflammatory challenge at different differentiation stages. GS expression at the late stages of differentiation desensitized mature adipocytes to bacterial lipopolysaccharide (LPS) by increasing intracellular glutamine levels. Furthermore, LPS-activated mature adipocytes were unable to produce inflammatory mediators; LPS sensitivity was rescued following GS inhibition and the associated drop in intracellular glutamine levels. The ability of adipocytes to differentially respond to LPS during differentiation negatively correlates to GS expression and intracellular glutamine levels. Hence, modulation of intracellular glutamine levels by GS expression represents an endogenous mechanism through which mature adipocytes control the inflammatory response.

Keywords: Adipocyte; Glutamine; Glutamine synthetase; Inflammation; Metabolic syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology*
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Animals
  • Cell Differentiation / drug effects*
  • Cell Line
  • Gene Expression Regulation, Enzymologic / drug effects
  • Glutamate-Ammonia Ligase / metabolism*
  • Glutamine / metabolism*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism*
  • Lipopolysaccharides / pharmacology*
  • Mice
  • Signal Transduction / drug effects

Substances

  • Lipopolysaccharides
  • Glutamine
  • Glutamate-Ammonia Ligase