ACSL4 promotes microglia-mediated neuroinflammation by regulating lipid metabolism and VGLL4 expression

Brain Behav Immun. 2023 Mar:109:331-343. doi: 10.1016/j.bbi.2023.02.012. Epub 2023 Feb 14.

Abstract

Acyl-CoA synthetase long-chain family member 4 (ACSL4) is an important isozyme in polyunsaturated fatty acid (PUFA) metabolism. The role of ACSL4 in the lipopolysaccharide (LPS)-induced inflammation of microglia, and the effects of ACSL4-mediated inflammation on the progression of Parkinson's disease (PD) are unknown. In this study, we found that ACSL4 expression was increased after LPS stimulation. Knocking down ACSL4 in microglia decreased proinflammatory cytokine production. Mechanistically, ACSL4 reduced vestigial-like family member 4(VGLL4) expression to promote NF-κB signal transduction; and ACSL4 regulated lipid composition after LPS stimulation. In addition, knocking down ACSL4 alleviated neuroinflammation in a systemic LPS model and acute l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) model. These data revealed ACSL4 to be a novel regulator that promotes microglia-mediated neuroinflammation by regulating VGLL4 expression and lipid metabolism.

Keywords: ACSL4; LPS; Lipid metabolism; Microglia; Neuroinflammation; PD; VGLL4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Coenzyme A Ligases
  • Disease Models, Animal
  • Inflammation / metabolism
  • Lipid Metabolism
  • Lipopolysaccharides / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microglia* / metabolism
  • Neuroinflammatory Diseases*
  • Transcription Factors / metabolism

Substances

  • Lipopolysaccharides
  • Acsl4 protein, mouse
  • Coenzyme A Ligases
  • VGLL4 protein, mouse
  • Transcription Factors