Biochanin A ameliorated oleate‐induced steatosis in HepG2 cells by activating the SIRT3/AMPK/ULK‐1 signaling pathway. Issue 12 (20th September 2022)

• Record Type: Journal Article
• Authors: Wang, Guo‐En; Liu, Xiao‐Ting; Yang, Fan; Wang, Ruo‐Hong; Liu, Xin‐Yu; Lv, Xi‐Ting; Lin, Xiao‐Li; Chen, Yan‐Fen
• Is Part Of: Journal of food biochemistry. Volume 46:Issue 12(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-09-20
• Subjects: adipocyte differentiation‐related protein -- autophagy -- chickpea -- hepatic steatosis -- LC3 -- p62; Food -- Analysis -- Periodicals; Food -- Composition -- Periodicals; Biochemistry -- Periodicals; 664.024
• DOI: 10.1111/jfbc.14428
• Languages: English
• ISSNs: 0145-8884

Abstract

Abstract: Biochanin A (Bio‐A), an isoflavone abundant in chickpeas, possesses hypoglycemic, hypolipidemic, and anti‐inflammatory effects. However, whether Bio‐A has antihepatosteatosis effect remains unclear. This study aimed to evaluate the antihepatosteatosis effect of Bio‐A on oleate (OA)‐treated hepatocytes, and explore the underlying mechanism. When incubated with OA for 24 h, HepG2 cells were treated with various concentrations of Bio‐A for 24 h to obtain an optimal antihepatosteatosis dose. HepG2 cells were treated with the AMP‐activated protein kinase (AMPK) inhibitor Compound C, or the sirtuin‐3 (SIRT3) inhibitor 3‐TYP, and incubated with 50 μM Bio‐A. The results indicated that 12.6% of lipid content, particularly 11.0% of triglyceride content, and the expression of adipocyte differentiation‐related protein were significantly decreased in Bio‐A‐treated hepatosteatosis cells, followed by an increase in the expression of Beclin 1, phosphorylation of Unc‐51‐like kinase 1 (ULK‐1), the microtubule‐associated protein 1 light chain 3 (LC3)‐II/LC3‐I ratio, and a decrease in expression of p62. The results indicated that Bio‐A upregulated autophagosome formation and autophagy flux. In addition, Bio‐A increased SIRT3 expression and AMPK phosphorylation in OA‐treated HepG2 cells. Blockade of AMPK and SIRT3 blocked the antihepatosteatosis effect and ULK‐1 activation by Bio‐A. AMPK inhibition did not eliminate the activation of SIRT3 by Bio‐A. AutoDock analysis demonstrated that interaction might exist between Bio‐A and SIRT3. In conclusion, Bio‐A reduced fat accumulation in OA‐treated HepG2 cells by activating SIRT3/AMPK/ULK‐1‐mediated autophagy. The findings provide a theoretical basis for the effect of Bio‐A on hepatic steatosis‐related diseases. Practical applications: This study highlights the antihepatosteatosis effects of biochanin A (Bio‐A) on oleate (OA)‐treated hepatocytes. Bio‐A, one of the isoflavones in Cicer arietinum Linn., possesses multiple bioactivities such as antiobesity, anti‐inflammation, and hypoglycemic and hypolipidemic effects. This study provides a new application of Bio‐A to treat hepatic steatosis, and revealed the underlying mechanism of Bio‐A involved in the activation of the SIRT3/AMPK/ULK‐1‐mediated autophagy. The findings provide a theoretical basis for the application of Bio‐A to hepatic steatosis‐related diseases. Abstract : Biochanin A reduces the fat accumulation in OA‐treated HepG2 cells by activating SIRT3/AMPK/ULK‐1‐mediated autophagy. This study provides a theoretical basis for the effect of Bio‐A on hepatic steatosis‐related diseases.