Fucoidan reduces lipid accumulation by promoting foam cell autophagy via TFEB

Carbohydr Polym. 2021 Sep 15:268:118247. doi: 10.1016/j.carbpol.2021.118247. Epub 2021 May 26.

Abstract

Atherosclerotic cardiovascular disease became one of the major causes of morbidity and mortality worldwide. As a sulfated polysaccharide with anti-inflammatory and hypolipidemic activities, fucoidan can induce autophagy. We show here that fucoidan reduces lipid accumulation in foam cells, which is one of the causes of atherosclerosis. Further studies show that fucoidan promotes autophagy showed by the expression of p62/SQSTM1 and microtubule-associated protein light chain 3 (LC3) II, which can be blocked by autophagy inhibitors 3-MA and bafilomycin A1. In addition, the expression of transcription factor EB (TFEB), master regulator of autophagy and lysosome function, is upregulated after the treatment with fucoidan. Moreover, the knockout of TFEB with small interfering RNA suppressed the effect of fucoidan. Together, fucoidan reduces lipid accumulation in foam cells by enhancing autophagy through the upregulation of TFEB. In view of the role of foam cells in atherosclerosis, fucoidan can be valuable for the treatment of atherosclerosis.

Keywords: Atherosclerosis; Autophagy; Foam cell; Fucoidan; Transcription factor EB.

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Animals
  • Autophagy / drug effects*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
  • Cell Survival / drug effects
  • Foam Cells / drug effects*
  • Lipid Metabolism / drug effects*
  • Lipoproteins, LDL / pharmacology
  • Macrolides / pharmacology
  • Mice
  • Polysaccharides / pharmacology*
  • RAW 264.7 Cells

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Lipoproteins, LDL
  • Macrolides
  • Polysaccharides
  • Tcfeb protein, mouse
  • oxidized low density lipoprotein
  • 3-methyladenine
  • bafilomycin A1
  • fucoidan
  • Adenine