Metformin reduces saturated fatty acid-induced lipid accumulation and inflammatory response by restoration of autophagic flux in endothelial cells

Academic Article


  • Autophagy, an integral part of the waste recycling process, plays an important role in cellular physiology and pathophysiology. Impaired autophagic flux causes ectopic lipid deposition, which is defined as the accumulation of lipids in non-adipose tissue. Ectopic lipid accumulation is observed in patients with cardiometabolic syndrome, including obesity, diabetes, insulin resistance, and cardiovascular complications. Metformin is the first line of treatment for type 2 diabetes, and one of the underlying mechanisms for the anti-diabetic effect of metformin is mediated by the stimulation of AMP-activated protein kinase (AMPK). Because the activation of AMPK is crucial for the initiation of autophagy, we hypothesize that metformin reduces the accumulation of lipid droplets by increasing autophagic flux in vascular endothelial cells. Incubation of vascular endothelial cells with saturated fatty acid (SFA) increased the accumulation of lipid droplets and impaired autophagic flux. We observed that the accumulation of lipid droplets was reduced, and the autophagic flux was enhanced by treatment with metformin. The knock-down of AMPKα by using siRNA blunted the effect of metformin. Furthermore, treatment with SFA or inhibition of autophagy increased leukocyte adhesion, whereas treatment with metformin decreased the SFA-induced leukocyte adhesion. The results suggest a novel mechanism by which metformin protects vascular endothelium from SFA-induced ectopic lipid accumulation and pro-inflammatory responses. In conclusion, improving autophagic flux may be a therapeutic strategy to protect endothelial function from dyslipidemia and diabetic complications.
  • Published In

  • Scientific Reports  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 21252748
  • Author List

  • Kim HS; Ren G; Kim T; Bhatnagar S; Yang Q; Bahk YY; Kim JA
  • Volume

  • 10
  • Issue

  • 1