Silibinin Restores NAD+ Levels and Induces the SIRT1/AMPK Pathway in Non-Alcoholic Fatty Liver
AbstractNicotinamide adenine dinucleotide (NAD+) homeostasis is emerging as a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and is tightly linked to the SIRT1/5’-AMP-activated protein kinase (AMPK) pathway. Silibinin, the main component of silymarin, has been proposed as a nutraceutical for the treatment of NAFLD. In this study, we aimed to identify whether silibinin may influence the NAD+/SIRT1 axis. To this end, C57BL/6 mice were fed a high fat diet (HFD) for 16 weeks, and were treated with silibinin or vehicle during the last 8 weeks. HepG2 cells were treated with 0.25 mM palmitate for 24 h with silibinin 25 µM or vehicle. HFD and palmitate administration led to oxidative stress, poly-(ADP-ribose)-polymerase (PARP) activation, NAD+ consumption, and lower SIRT1 activity. In mice fed the HFD, and in HepG2 treated with palmitate, we consistently observed lower levels of phospho-AMPKThr172 and phospho-acetyl-CoA carboxylaseSer79 and higher levels of nuclear sterol regulatory element-binding protein 1 activity, indicating de novo lipogenesis. Treatment of mice and HepG2 with silibinin abolished oxidative stress, and inhibited PARP activation thus restoring the NAD+ pool. In agreement with preserved NAD+ levels, SIRT1 activity and AMPK phosphorylation returned to control levels in mice and HepG2. Our results further indicate silibinin as a promising molecule for the treatment of NAFLD. View Full-Text
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Salomone, F.; Barbagallo, I.; Godos, J.; Lembo, V.; Currenti, W.; Cinà, D.; Avola, R.; D’Orazio, N.; Morisco, F.; Galvano, F.; Li Volti, G. Silibinin Restores NAD+ Levels and Induces the SIRT1/AMPK Pathway in Non-Alcoholic Fatty Liver. Nutrients 2017, 9, 1086.
Salomone F, Barbagallo I, Godos J, Lembo V, Currenti W, Cinà D, Avola R, D’Orazio N, Morisco F, Galvano F, Li Volti G. Silibinin Restores NAD+ Levels and Induces the SIRT1/AMPK Pathway in Non-Alcoholic Fatty Liver. Nutrients. 2017; 9(10):1086.Chicago/Turabian Style
Salomone, Federico; Barbagallo, Ignazio; Godos, Justyna; Lembo, Vincenzo; Currenti, Walter; Cinà, Diana; Avola, Roberto; D’Orazio, Nicolantonio; Morisco, Filomena; Galvano, Fabio; Li Volti, Giovanni. 2017. "Silibinin Restores NAD+ Levels and Induces the SIRT1/AMPK Pathway in Non-Alcoholic Fatty Liver." Nutrients 9, no. 10: 1086.