Pomegranate juice protects macrophages from triglyceride accumulation: inhibitory effect on DGAT1 activity and on triglyceride biosynthesis.

To analyze the effects of pomegranate juice (PJ) and punicalagin on macrophage triglyceride metabolism. 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. 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. We conclude that the inhibitory effect of PJ on triglyceride biosynthesis could be attributed to a direct effect of PJ on DGAT1 activity.