title: Pomegranate juice protects macrophages from triglyceride accumulation: inhibitory effect on DGAT1 activity and on triglyceride biosynthesis.
abstract: OBJECTIVE
  To analyze the effects of pomegranate juice (PJ) and punicalagin on macrophage triglyceride metabolism.
  
  
  METHODS
  Triglyceride metabolism was analyzed in PJ- or punicalagin-treated J774A.1 macrophages or in mouse peritoneal macrophages (MPM) harvested from C57BL/6 mice or from paraoxonase 2 (PON2)-deficient mice.
  
  
  RESULTS
  PJ (0-50 μM) significantly and dose-dependently decreased the triglyceride content and triglyceride biosynthesis rate in J774A.1 macrophages or in C57BL/6 MPM by about 30%. Similarly, punicalagin, the major PJ polyphenol, inhibited the MPM triglyceride biosynthesis rate by 40%. The triglyceride hydrolytic rate, however, was not significantly affected by PJ or punicalagin. The activity of diacylglycerol acyltransferase 1 (DGAT1; the rate-limiting enzyme in triglyceride biosynthesis) was significantly inhibited, by 54%, in C57BL/6 MPM that were treated with 50 μM PJ or punicalagin, with no significant effect on DGAT1 mRNA or protein expression. Both PJ and punicalagin increased (1.7-fold) MPM PON2 mRNA expression, and PON2 was previously shown to inhibit DGAT1 activity. However, the addition of PJ or punicalagin (50 μM) to microsomes from PON2-deficient MPM still resulted in a significant reduction (50-58%) in DGAT1 activity.
  
  
  CONCLUSIONS
  We conclude that the inhibitory effect of PJ on triglyceride biosynthesis could be attributed to a direct effect of PJ on DGAT1 activity.
authors.affiliation: The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, Rambam Medical Center, Haifa, Israel.
authors.forename: Mira
authors.initials: M
authors.lastname: Rosenblat
authors.forename: Michael
authors.initials: M
authors.lastname: Aviram
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D043303:Aryldialkylphosphatase / Q000378:metabolism; D001628:Beverages; D002460:Cell Line; D051048:Diacylglycerol O-Acyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D029561:Lythraceae / Q000737:chemistry*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D014280:Triglycerides / Q000096:biosynthesis*
chemical_list: D000975:Antioxidants; D047348:Hydrolyzable Tannins; D014280:Triglycerides; C115642:punicalagin; C494882:Dgat1 protein, mouse; D051048:Diacylglycerol O-Acyltransferase; D043303:Aryldialkylphosphatase