title: Sesamol and sesame (Sesamum indicum) oil enhance macrophage cholesterol efflux via up-regulation of PPARγ1 and LXRα transcriptional activity in a MAPK-dependent manner.
abstract: OBJECTIVE
  Cholesterol clearance by macrophages is a vital process to eliminate excess cholesterol from the body. Internalization of modified cholesterol by macrophages triggers overexpression of peroxisome proliferator-activated receptor γ1 (PPARγ1) and liver X receptor α (LXRα), two transcription factors that are critically involved in macrophage cholesterol efflux. Recent studies demonstrate that oral administration of sesamol derivative (INV-403) and sesame oil leads to a significant attenuation of atherosclerosis in Watanabe heritable hyperlipidemic rabbits and LDLR(-/-) mice, respectively. However, the exact molecular mechanisms underlying such anti-atherogenic effects remain largely unrevealed.
  
  
  METHODS
  Luciferase reporter assays were performed to assess the effects of sesamol and sesame oil on PPARγ1 and LXRα gene expression. The potential of sesamol and sesame oil to modulate cholesterol efflux was evaluated using (3)H-cholesterol efflux assays.
  
  
  RESULTS
  Sesamol and sesame oil treatments lead to a significant up-regulation of PPARγ1 and LXRα expression and transcriptional activity in a MAPK-dependent manner. Importantly, primary macrophages display a significantly enhanced cholesterol efflux potential upon treatment with sesamol and sesame oil, and this stimulatory effect is mediated by MAPK signaling.
  
  
  CONCLUSIONS
  Our findings suggest that the previously reported anti-atherogenic effects of sesamol and sesame oil could be attributed, at least in part, to enhanced PPARγ1 and LXRα expression and transcriptional activity leading to improved macrophage cholesterol efflux. Our study is novel in elucidating the molecular and cellular mechanisms underlying the protective effects of sesamol and sesame oil against atherosclerosis.
authors: Department of Biology, Chemistry and Environmental Sciences, College of Arts and Sciences, American University of Sharjah, P.O. Box 26666, Sharjah, United Arab Emirates, amajdalawieh@aus.edu.
authors: Amin F
authors: AF
authors: Majdalawieh
authors: Hyo-Sung
authors: HS
authors: Ro
mesh_terms: D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology*; D016466:CHO Cells; D002784:Cholesterol / Q000378:metabolism*; D003412:Cricetulus; D006949:Hyperlipidemias / Q000188:drug therapy; D000071518:Liver X Receptors; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology*; D011817:Rabbits; D012715:Sesame Oil / Q000494:pharmacology*; D031685:Sesamum / Q000737:chemistry*; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D052117:Benzodioxoles; D000071518:Liver X Receptors; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D010636:Phenols; D012715:Sesame Oil; C025583:sesamol; D002784:Cholesterol