Huang, S.; Zhang, B.; Chen, Y.; Liu, H.; Liu, Y.; Li, X.; Bao, Z.; Song, Z.; Wang, Z. Inhibition of PARP Activity Attenuated Hepatic Triglyceride Accumulation in Alcoholic Fatty Liver Disease in Mice. Preprints2017, 2017040144. https://doi.org/10.20944/preprints201704.0144.v1
APA Style
Huang, S., Zhang, B., Chen, Y., Liu, H., Liu, Y., Li, X., Bao, Z., Song, Z., & Wang, Z. (2017). Inhibition of PARP Activity Attenuated Hepatic Triglyceride Accumulation in Alcoholic Fatty Liver Disease in Mice. Preprints. https://doi.org/10.20944/preprints201704.0144.v1
Chicago/Turabian Style
Huang, S., Zhenyuan Song and Zhigang Wang. 2017 "Inhibition of PARP Activity Attenuated Hepatic Triglyceride Accumulation in Alcoholic Fatty Liver Disease in Mice" Preprints. https://doi.org/10.20944/preprints201704.0144.v1
Abstract
The specific role of nicotinamide adenine dinucleotide (NAD) in hepatic triglyceride (TG) accumulation in alcoholic fatty liver disease (AFLD) were unclear. Poly ADP ribose polymerase (PARP) is a NAD-consuming enzyme and its specific role in the pathogenesis of AFLD is still elusive. In current investigation, we found that chronic alcohol exposure enhanced hepatic PARP expression and activity and lowered hepatic NAD+ level. PARP activity inhibitor 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 observation was validated in alcohol-fed mice injected with PJ34 intraperitoneally. PJ34 injection attenuated hepatic TG accumulation in alcohol-fed mice. Further, 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. At last, 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 might be a potential candidate for AFLD therapy.
Biology and Life Sciences, Biology and Biotechnology
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