Chlamydia pneumoniae exploits adipocyte lipid chaperone FABP4 to facilitate fat mobilization and intracellular growth in murine adipocytes

Biochem Biophys Res Commun. 2018 Jan 1;495(1):353-359. doi: 10.1016/j.bbrc.2017.11.005. Epub 2017 Nov 3.

Abstract

Fatty acid-binding protein 4 (FABP4), a cytosolic lipid chaperone predominantly expressed in adipocytes and macrophages, modulates lipid fluxes, trafficking, signaling, and metabolism. Recent studies have demonstrated that FABP4 regulates metabolic and inflammatory pathways, and in mouse models its inhibition can improve type 2 diabetes mellitus and atherosclerosis. However, the role of FABP4 in bacterial infection, metabolic crosstalk between host and pathogen, and bacterial pathogenesis have not been studied. As an obligate intracellular pathogen, Chlamydia pneumoniae needs to obtain nutrients such as ATP and lipids from host cells. Here, we show that C. pneumoniae successfully infects and proliferates in murine adipocytes by inducing hormone sensitive lipase (HSL)-mediated lipolysis. Chemical inhibition or genetic manipulation of HSL significantly abrogated the intracellular growth of C. pneumoniae in adipocytes. Liberated free fatty acids were utilized to generate ATP via β-oxidation, which C. pneumoniae usurped for its replication. Strikingly, chemical inhibition or genetic silencing of FABP4 significantly abrogated C. pneumoniae infection-induced lipolysis and mobilization of liberated FFAs, resulting in reduced bacterial growth in adipocytes. Collectively, these results demonstrate that C. pneumoniae exploits host FABP4 to facilitate fat mobilization and intracellular replication in adipocytes. This work uncovers a novel strategy used by intracellular pathogens for acquiring energy via hijacking of the host lipid metabolism pathway.

Keywords: Adipocytes; Chlamydia pneumoniae; Fatty acid-binding protein 4; Infection; Lipolysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / microbiology*
  • Adipocytes / physiology*
  • Animals
  • Cell Proliferation / physiology
  • Chlamydophila pneumoniae / cytology
  • Chlamydophila pneumoniae / physiology*
  • Fatty Acid-Binding Proteins / metabolism*
  • Lipid Mobilization / physiology*
  • Mice
  • Sterol Esterase / metabolism*

Substances

  • Fabp4 protein, mouse
  • Fatty Acid-Binding Proteins
  • Sterol Esterase