title: Autophagy involved in lipopolysaccharide-induced foam cell formation is mediated by adipose differentiation-related protein.
abstract: BACKGROUND
  Autophagy is an essential process for breaking down macromolecules and aged/damaged cellular organelles to maintain cellular energy balance and cellular nutritional status. The idea that autophagy regulates lipid metabolism is an emerging concept with important implications for atherosclerosis. However, the potential role of autophagy and its relationship with lipid metabolism in foam cell formation remains unclear. In this study, we found that autophagy was involved in the lipopolysaccharide (LPS)-induced the formation of foam cells and was at least partially dependent on adipose differentiation-related protein (ADRP).
  
  
  METHODS
  Foam cell formation was evaluated by Oil red O staining. Autophagic activity was determined by immunofluorescence and Western blotting. ADRP gene expression of ADRP was examined by real-time PCR (RT-PCR). The protein expression of ADRP and LC3 was measured using Western blotting analysis. Intracellular cholesterol and triglyceride levels in foam cells were quantitatively measured by enzymatic colorimetric assays.
  
  
  RESULTS
  LPS promoted foam cell formation by inducing lipid accumulation in macrophages. The activation of autophagy with rapamycin (Rap) decreased intracellular cholesterol and triglyceride levels, whereas the inhibition of autophagy with 3-methyladenine (3MA) enhanced the accumulation of lipid droplets. Overexpression of ADRP alone increased the formation of foam cells and consequently autophagic activity. In contrast, the inhibitory effects of ADRP activity with siRNA suppressed the activation of autophagy. Taken together, we propose a novel role for ADRP in the regulation of macrophage autophagy during LPS stimulation.
  
  
  CONCLUSIONS
  We defined a new molecular pathway in which LPS-induced foam cell formation is regulated through autophagy. These findings facilitate the understanding of the role of autophagy in the development of atherosclerosis.
authors.forename: Xuyang
authors.initials: X
authors.lastname: Feng
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.forename: Zuyi
authors.initials: Z
authors.lastname: Yuan
authors.forename: Xiumin
authors.initials: X
authors.lastname: Zhang
authors.forename: Wen
authors.initials: W
authors.lastname: Sui
authors.forename: Peizhen
authors.initials: P
authors.lastname: Hu
authors.forename: Pengfei
authors.initials: P
authors.lastname: Zheng
authors.affiliation: Department of Pathology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China. yejing1219@gmail.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Ye
mesh_terms: D001343:Autophagy / Q000276:immunology*; D002460:Cell Line; D005487:Foam Cells / Q000276:immunology*; D055785:Gene Knockdown Techniques; D006801:Humans; D050356:Lipid Metabolism / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008565:Membrane Proteins / Q000502:physiology*; D000070780:Perilipin-2; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D008070:Lipopolysaccharides; D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D000070780:Perilipin-2; D034741:RNA, Small Interfering