Blockage of NDUFB9-SCD1 pathway inhibits adipogenesis Blockage of NDUFB9-SCD1 pathway inhibits adipogenesis

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with an increasing global prevalence associated with tremendous clinical, economic, and health-related quality-of-life burden. Currently, no effective pharmacological therapy is available for NAFLD. Adipogenesis process is accompanied by fat synthesis which may participate in the occurrence and development of NAFLD. Despite intensive investigations, numerous mechanistic aspects of adipogenesis remain unclear and many potential therapeutic targets are yet to be discovered. In this study, the transcriptomics and lipidomics approaches were used to explore the functional genes regulating adipogenesis and the potential mechanism in OP9 cells and adipose-derived stem cells. We find that NADH:ubiquinone oxidoreductase subunit b9 (Ndufb9) is up-regulated in adipogenesis (p < 0.001), and silencing Ndufb9 (83% silencing efficiency) inhibits adipogenesis. The effect of Ndufb9 is mediated through stearoyl-CoA desaturase 1 (Scd1). Aramchol, a SCD1 inhibitor, significantly blocks adipogenesis (markedly TG decrease, p < 0.001). Our study broadens the understanding of the role of Ndufb9 in adipogenesis and provides a new target for the treatment of NAFLD.

Automated summary

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with a global prevalence that is increasing. Currently, there is no effective pharmacological therapy available for NAFLD. In this study, the role of Ndufb9 in adipogenesis and its potential as a target for NAFLD treatment were explored. It was found that Ndufb9 is up-regulated in adipogenesis and its effect is mediated through Scd1. Additionally, the inhibition of Scd1 by aramchol significantly blocks adipogenesis. These findings provide new insights into the understanding and treatment of NAFLD.