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Royal jelly fatty acids downregulate ANGPTL8 expression through the decrease in HNF4α protein in human hepatoma HepG2
Yuki Inoue1, Marina Ienaga1, Tetsuro Kamiya1
1Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, Japan.
Bioscience, Biotechnology, and Biochemistry
|March 24, 2022
Summary
Sebacic acid (SA), found in royal jelly, reduces serum lipids by decreasing Angiopoietin-like protein 8 (ANGPTL8) expression. This occurs through reduced activity of the transcription factor HNF4α, impacting lipid metabolism.
Area of Science:
- Biochemistry
- Molecular Biology
- Nutraceuticals
Background:
- Royal jelly (RJ) is known to reduce serum lipids, but the underlying mechanisms are unclear.
- Angiopoietin-like protein 8 (ANGPTL8) is a key regulator of lipid metabolism.
- Specific fatty acids in RJ may influence lipid-lowering effects.
Purpose of the Study:
- To investigate the effect of RJ fatty acids on ANGPTL8 expression in liver cells.
- To elucidate the molecular mechanism by which sebacic acid (SA) affects ANGPTL8.
Main Methods:
- Human hepatoma HepG2 cells were treated with RJ fatty acids, including SA.
- Reporter assays were used to assess ANGPTL8 promoter activity.
- Hepatocyte nuclear factor-4α (HNF4α) binding and protein levels were analyzed.
- Small interfering RNA (siRNA) was used to knock down HNF4α.
Main Results:
- Sebacic acid significantly reduced ANGPTL8 expression and promoter activity.
- SA decreased HNF4α protein levels and its binding to the ANGPTL8 promoter.
- HNF4α knockdown led to suppressed ANGPTL8 mRNA expression.
Conclusions:
- Sebacic acid downregulates ANGPTL8 expression in liver cells.
- This downregulation is mediated by a reduction in HNF4α protein levels and activity.
- SA's effect on ANGPTL8 offers a potential mechanism for RJ's lipid-lowering benefits.
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