Purple sweet potato color protects against hepatocyte apoptosis through Sirt1 activation in high-fat-diet-treated mice

Weitong Su; Cheng Zhang; Feng Chen; Junwen Sui; Jiaqi Lu; Qingqing Wang; Qun Shan; Guihong Zheng; Jun Lu; Chunhui Sun; Shaohua Fan; Dongmei Wu; Zifeng Zhang; Yuanlin Zheng

doi:10.29219/fnr.v64.1509

Purple sweet potato color protects against hepatocyte apoptosis through Sirt1 activation in high-fat-diet-treated mice

Food Nutr Res. 2020 Feb 4:64. doi: 10.29219/fnr.v64.1509. eCollection 2020.

Authors

Weitong Su¹, Cheng Zhang¹, Feng Chen¹, Junwen Sui¹, Jiaqi Lu¹, Qingqing Wang¹, Qun Shan¹, Guihong Zheng¹, Jun Lu¹, Chunhui Sun¹, Shaohua Fan¹, Dongmei Wu¹, Zifeng Zhang¹, Yuanlin Zheng¹

Affiliation

¹ Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, College of Health Science, Jiangsu Normal University, Xuzhou, Jiangsu Province, P. R. China.

Abstract

Background: Recent evidence indicates that the inhibition of hepatocyte apoptosis is possible to develop a potential therapeutic strategy for nonalcoholic fatty liver disease (NAFLD). Our previous work suggested that purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, effectively improved many features of high-fat diet (HFD)-induced NAFLD. However, whether PSPC ameliorates HFD-induced hepatocyte apoptosis has never been investigated.

Objective: Here we investigated the effects of PSPC on HFD-induced hepatic apoptosis and the mechanisms underlying these effects.

Design: Mice were divided into four groups: Control group, HFD group, HFD + PSPC group and PSPC group. PSPC was administered by daily oral gavage at doses of 700 mg/kg/day for 20 weeks. EX-527 (a SirT1-selective inhibitor) and Sirt1 siRNA were used to demonstrate the Sirt1 dependence of PSPC-mediated effects on apoptotic and survival signaling pathways in vivo and in vitro.

Results: Our results showed that PSPC reduced body weights, hepatic triglyceride contents, histopathological lesions and serum ALT levels in a mouse model of NAFLD induced by HFD. Furthermore, PSPC attenuated HFD-induced hepatocyte apoptosis ratio from 7.27 ± 0.92% to 1.79 ± 0.27% in mouse livers, which is insignificant compared with that of controls. Moreover, PSPC activated Sirt1 by boosting NAD⁺ level in HFD-treated mouse livers. Furthermore, PSPC promoted Sirt1-dependent suppression of P53-mediated apoptotic signaling and activation of Akt survival signaling pathway in HFD-treated mouse livers, which was confirmed by EX527 treatment. Moreover, Sirt1 knockdown abolished these ameliorative effects of PSPC on apoptosis and P53 acetylation and protein expression in PA-treated L02 cells. Ultimately, PSPC reduced Caspase-3 activation and Bax level, and elevated the Bcl-2 level in HFD-treated mouse livers.

Conclusion: PSPC protected against HFD-induced hepatic apoptosis by promoting Sirt1- dependent inhibition of p53-apoptotic pathway and facilitation of Akt survival pathway. This study indicates that PSPC is a candidate for nutritional intervention of NAFLD.

Keywords: Akt; P53; Sirt1; hepatic apoptosis; high-fat diet; purple sweet potato color.