Liquiritigenin Inhibits Lipid Accumulation in 3T3-L1 Cells via mTOR-Mediated Regulation of the Autophagy Mechanism

Abstract

Liquiritigenin (LQG) is a natural flavonoid from the herb Glycyrrhiza uralensis Fisch that exhibits multiple biological activities. However, its specific role in antiobesity and its related underlying molecular mechanisms remain unknown. The primary purpose of this study is to explore the effects and regulatory mechanisms of LQG on lipid accumulation in 3T3-L1 adipocytes. The results show that LQG significantly reduced triglyceride levels and downregulated the expression of transcription factors such as CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) in 3T3-L1 adipocytes. Additionally, the expression of sterol-regulatory element-binding protein 1c (SREBP1c), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FASN) involved in lipogenesis was reduced by treatment with LQG. The protein expression levels of light chain 3B (LC3B), autophagy-related protein 7 (ATG7) and p62 were also modulated by LQG, leading to the suppression of autophagy. Further, LQG activated the phosphorylation of the mammalian target of rapamycin (mTOR), the inhibition of which was followed by the restored expression of autophagy-related proteins. Pretreatment with an mTOR inhibitor also reverted the expression of several genes or proteins involved in lipid synthesis. These results suggest that LQG inhibited lipid accumulation via mTOR-mediated autophagy in 3T3-L1 white adipocytes, indicating the role of LQG as a potential natural bioactive component for use in dietary supplements for preventing obesity.

Liquiritigenin Confers Liver Protection by Enhancing NRF2 Signaling through Both Canonical and Non-canonical Signaling Pathways

“…Some studies suggest that LQ protects against drug-induced liver injury via inhibiting oxidative stress and enhancing mTOR-mediated autophagy, and the PI3K/AKT signaling pathway may be involved in the LQ-mediated autophagy . However, recent study reveals that LQ treatment induces mTOR signal and suppresses autophagy, which is similar to our current work. Our results indicate that the treatment with LQ inhibits the formation of autophagosome and autolysosome and blocks autophagic flux in liver cells, resulting in the accumulation of p62 and the upregulation of NRF2.…”

“…Some studies suggest that LQ protects against drug-induced liver injury via inhibiting oxidative stress and enhancing mTORmediated autophagy, 7 and the PI3K/AKT signaling pathway may be involved in the LQ-mediated autophagy. 41 However, recent study reveals that LQ treatment induces mTOR signal and suppresses autophagy, 42 which is similar to our current Moreover, the relationship between LQ-regulated genes and NRF2 transcription in the human liver tissue and hepatocellular carcinoma was analyzed using GEPIA (C,D). work.…”