Abstract

Fatty acid β-oxidation is an essential pathogenic mechanism in nonalcoholic fatty liver disease (NAFLD), and TATA-box binding protein associated factor 9 (TAF9) has been reported to be involved in the regulation of fatty acid β-oxidation. However, the function of TAF9 in NAFLD, as well as the mechanism by which TAF9 is regulated, remains unclear. In this study, we aimed to investigate the signaling mechanism underlying the involvement of TAF9 in NAFLD and the protective effect of the natural phenolic compound Danshensu (DSS) against NAFLD via the HDAC1/TAF9 pathway. An in vivo model of high-fat diet (HFD)-induced NAFLD and a palmitic acid (PA)-treated AML-12 cell model were developed. Pharmacological treatment with DSS significantly increased fatty acid β-oxidation and reduced lipid droplet (LD) accumulation in NAFLD. TAF9 overexpression had the same effects on these processes both in vivo and in vitro. Interestingly, the protective effect of DSS was markedly blocked by TAF9 knockdown. Mechanistically, TAF9 was shown to be deacetylated by HDAC1, which regulates the capacity of TAF9 to mediate fatty acid β-oxidation and LD accumulation during NAFLD. In conclusion, TAF9 is a key regulator in the treatment of NAFLD that acts by increasing fatty acid β-oxidation and reducing LD accumulation, and DSS confers protection against NAFLD through the HDAC1/TAF9 pathway.

Highlights

  • Nonalcoholic fatty liver disease (NAFLD), a chronic disease which affects over 25% of the global population (Younossi et al, 2016)

  • Our aims were as follows: 1) to explore whether TATA-box binding protein associated factor 9 (TAF9) can be involved in nonalcoholic fatty liver disease (NAFLD); 2) to explore the role of deacetylation of TAF9 by Histone deacetylase 1 (HDAC1) in NAFLD; and 3) to test whether DSS can alleviate NAFLD through the HDAC1/TAF9 signaling pathway

  • The results indicated that DSS attenuates NAFLD in rats

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Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD), a chronic disease which affects over 25% of the global population (Younossi et al, 2016). The clinical spectrum of NAFLD includes many kinds of diseases: steatohepatitis, fibrosis, and even cirrhosis and hepatocellular carcinoma (Estes et al, 2018). Danshensu Alleviates NAFLD via HDAC1/TAF9 study has demonstrated that fatty acid β-oxidation, which is one of the most important metabolic pathways of fatty acids (Li et al, 2014), plays an essential role in metabolic diseases progression such as insulin resistance, type 2 diabetes, atherosclerosis, dyslipidemia and NAFLD (Rogge et al, 2009). Exploring a target of NAFLD to increase fatty acid β-oxidation may provide therapeutic strategies for NAFLD

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