Exogenous (Pomegranate Juice) or Endogenous (Paraoxonase1) Antioxidants Decrease Triacylglycerol Accumulation in Mouse Cardiovascular Disease‐Related Tissues

: The polyphenol-rich pomegranate juice (PJ) and the high-density lipoprotein (HDL)-associated paraoxonase1 (PON1) are known as potent atheroprotective antioxidants, but their effects on other tissues related to cardiovascular disease (CVD) remain unknown. The current study aimed to investigate the effects of treating mice with PJ or recombinant PON1 (rePON1) on the oxidation and lipid status of CVD-related tissues: serum, aorta, heart, liver, kidney, visceral, and subcutaneous adipose tissues (VAT and SAT). Both PJ consumption and rePON1 injection decreased the serum levels of thiobarbituric acid-reactive substances (16% and 19%) and triacylglycerols (TAG, 24% and 27%), while only rePON1 increased the levels of thiol groups (35%) and decreased serum cholesterol (15%). Both PJ and rePON1 significantly decreased aortic cholesterol (38% and 32%) and TAG (62% and 58%) contents in association with downregulation of the key TAG biosynthetic enzyme diacylglycerol O-acyltransferase 1 (DGAT1, 71% and 65%), while only PJ decreased aortic lipid peroxides (47%). Substantial TAG-lowering effects of both PJ and rePON1 were observed also in the heart (31% and 42%), liver (34% and 42%), and kidney (42% and 57%). In both VAT and SAT, rePON1 decreased the levels of lipid peroxides (28% and 25%), while PJ decreased the TAG content (22% and 18%). Ex vivo incubation of SAT with serum derived from mice that consumed PJ or injected with rePON1 decreased SAT lipid peroxides (35% or 28%) and TAG mass (12% or 10%). These novel findings highlight potent TAG-lowering properties of exogenous (PJ) and endogenous (PON1) antioxidants in tissues associated with CVD.