Praeruptorin B improves diet-induced hyperlipidemia and alleviates insulin resistance via regulating SREBP signaling pathway

Abstract

Many metabolic diseases are caused by disruption of lipid homeostasis. Sterol regulatory element-binding proteins (SREBPs) are a family of nuclear transcription factors that are associated with lipid de novo synthesis, thereby, SREBPs have been considered as targets for the treatment of metabolic diseases. In this study, we identified praeruptorin B as a novel inhibitor of SREBPs. HepG2 cells were used to verify lipid-lowering effects of praeruptorin B. The expression of SREBPs, as well as their target genes was markedly suppressed. Furthermore, we found that praeruptorin B inhibits the proteins expression of SREBP by regulating PI3K/Akt/mTOR pathway. In praeruptorin B-treated high fat diet (HFD)-fed obese mice, HFD induced lipid deposition, hyperlipidemia and insulin resistance were significantly ameliorated, and SREBPs and related genes in liver were down-regulated. These findings suggest that praeruptorin B exerts lipid-lowering effects through SREBPs regulation and could serve as a possible therapeutic option to improve hyperlipidemia and hyperlipidemia-induced comorbidities.