Tanshinone IIA Downregulates Lipogenic Gene Expression and Attenuates Lipid Accumulation through the Modulation of LXR alpha/SREBP1 Pathway in HepG2 Cells

doi:10.3390/biomedicines9030326

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Title:	Tanshinone IIA Downregulates Lipogenic Gene Expression and Attenuates Lipid Accumulation through the Modulation of LXR alpha/SREBP1 Pathway in HepG2 Cells
Authors:	Gao, Wan-Yun Chen, Pei-Yi Hsu, Hao-Jen Lin, Ching-Yen Wu, Ming-Jiuan Yen, Jui-Hung
Contributors:	Tzu Chi Univ, Inst Med Sci Hualien Tzu Chi Hosp, Buddhist Tzu Chi Med Fdn, Ctr Med Genet Tzu Chi Univ, Dept Mol Biol & Human Genet Tzu Chi Univ, Dept Life Sci Chia Nan Univ Pharm & Sci, Dept Biotechnol
Keywords:	MAFLD tanshinone IIA phytochemical lipogenesis lipid accumulation LXR alpha
Date:	2021
Issue Date:	2023-11-11 11:53:49 (UTC+8)
Publisher:	MDPI
Abstract:	Abnormal and excessive accumulation of lipid droplets within hepatic cells is the main feature of steatosis and nonalcoholic fatty liver disease (NAFLD) or metabolic-associated fatty liver disease (MAFLD). Dysregulation of lipogenesis contributes to hepatic steatosis and plays an essential role in the pathological progress of MAFLD. Tanshinone IIA is a bioactive phytochemical isolated from Salvia miltiorrhiza Bunge and exhibits anti-inflammatory, antiatherosclerotic and antihyperlipidemic effects. In this study, we aimed to investigate the lipid-lowering effects of tanshinone IIA on the regulation of lipogenesis, lipid accumulation, and the underlying mechanisms in hepatic cells. We demonstrated that tanshinone IIA can significantly inhibit the gene expression involved in de novo lipogenesis including FASN, ACC1, and SCD1, in HepG2 and Huh 7 cells. Tanshinone IIA could increase phosphorylation of ACC1 protein in HepG2 cells. We further demonstrated that tanshinone IIA also could suppress the fatty-acid-induced lipogenesis and TG accumulation in HepG2 cells. Furthermore, tanshinone IIA markedly downregulated the mRNA and protein expression of SREBP1, an essential transcription factor regulating lipogenesis in hepatic cells. Moreover, we found that tanshinone IIA attenuated liver X receptor alpha (LXR alpha)-mediated lipogenic gene expression and lipid droplet accumulation, but did not change the levels of LXR alpha mRNA or protein in HepG2 cells. The molecular docking data predicted tanshinone IIA binding to the ligand-binding domain of LXR alpha, which may result in the attenuation of LXR alpha-induced transcriptional activation. Our findings support the supposition that tanshinone IIA possesses a lipid-modulating effect that suppresses lipogenesis and attenuates lipid accumulation by modulating the LXR alpha/SREBP1 pathway in hepatic cells. Tanshinone IIA can be potentially used as a supplement or drug for the prevention or treatment of MAFLD.
Relation:	BIOMEDICINES, v.9, n.3, pp.326
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Periodical Articles

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