TY - JOUR T1 - PARP Inhibitor PJ34 Attenuated Hepatic Triglyceride Accumulation in Alcoholic Fatty Liver Disease in Mice JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.117.243105 SP - jpet.117.243105 AU - Shishun Huang AU - Bing Zhang AU - Yingli Chen AU - Huan Liu AU - Yang Liu AU - Xin Li AU - Zhiwei Bao AU - Zhenyuan Song AU - Zhigang Wang Y1 - 2018/01/01 UR - http://jpet.aspetjournals.org/content/early/2018/01/09/jpet.117.243105.abstract N2 - Poly ADP ribose polymerase (PARP) is a NAD-consuming enzyme and its specific role in the pathogenesis of alcoholic fatty liver disease (AFLD) is still elusive. In current study, we applied PJ34 to inhibit hepatic PARP activity to examine the corresponding pathological alteration in AFLD in mice and the underlying molecular mechanism. We found that PJ34 decreased the intracellular TG content in hepatocyte. Moreover, PJ34 suppressed the gene expression of DGAT1 and DGAT2 and elevated the intracellular NAD+ level in hepatocyte. These mechanistic observations were validated in alcohol-fed mice injected with PJ34 intraperitoneally. Results indicate that the PJ34 injection attenuated hepatic TG accumulation in alcohol-fed mice. Furthermore, the gene expression of hepatic SERBP-1c, DGAT1 and DGAT2 were lowered by PJ34 injection, while the hepatic NAD+ level was augmented by PJ34 injection in alcohol-fed mice. Finally, the nicotinamide riboside supplementation alleviated hepatic TG accumulation in alcohol-fed mice. These data indicate that applying PARP specific inhibitor PJ34 by intraperitoneal injection attenuated hepatic NAD+ depletion and TG accumulation in alcohol-fed mice, which may be a potential candidate for AFLD therapy. ER -