Oleic acid-induced defective autolysosome shows impaired lipid degradation

Biochem Biophys Res Commun. 2019 Jun 4;513(3):553-559. doi: 10.1016/j.bbrc.2019.04.040. Epub 2019 Apr 10.

Abstract

Recent studies suggest an alternative pathway of lipid breakdown called lipophagy, which delivers lipid droplets (LDs) to lysosomes for degradation of LDs. However, molecular mechanisms regulating lipophagy are still largely unknown. In this study, we evaluated the effect of oleic acid (OA) on lipophagy in cells. We found that OA treatment results in accumulation of p62 and LC3-II proteins and reduces red fluorescence in cells stably expressing mCherry-GFP-LC3. In addition, OA inhibits the co-localization of LC3 with LAMP1 under serum-deprived condition, suggesting that OA blocks autophagosome-lysosome fusion. In the cells with ATG5 or ULK1 gene deletion, LDs did not increase upon OA treatment more than in wild type cells. However, cell starvation following OA removal resulted in reduced lipid accumulation by lipophagy and recovery of autophagy flux, suggesting that the specific condition of OA treatment and cell starvation are important for lipophagy flux activity.

Keywords: Autophagy; Lipid droplets; Lipophagy; Lysosome; Oleic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagosomes / drug effects
  • Autophagosomes / metabolism
  • Autophagy / drug effects*
  • Cell Line
  • Hep G2 Cells
  • Humans
  • Lipid Droplets / metabolism
  • Lipolysis / drug effects*
  • Lysosomes / drug effects*
  • Lysosomes / metabolism
  • Mice
  • Oleic Acid / pharmacology*

Substances

  • Oleic Acid