Dietary flavones counteract phorbol 12-myristate 13-acetate-induced SREBP-2 processing in hepatic cells

Area of Science:

• Biochemistry
• Molecular Biology
• Nutritional Science

Background:

• Dietary fruits and vegetables positively impact plasma lipid profiles.
• The precise mechanisms behind these beneficial effects remain largely unknown.
• Sterol regulatory element-binding protein 2 (SREBP-2) is a key regulator of cholesterol biosynthesis, controlling the HMGCR enzyme.

Purpose of the Study:

• To investigate the AMPK-independent signaling pathway through which apigenin and luteolin affect SREBP-2 processing.
• To determine the efficacy of apigenin and luteolin in modulating cholesterol metabolism in hepatic cells.
• To explore the potential physiological implications of these findings.

Main Methods:

• Utilized hepatic cell lines (WRL and HepG2) treated with phorbol 12-myristate 13-acetate (PMA).
• Assessed SREBP-2 processing and nuclear translocation using EMSA and immunocytochemistry.
• Quantified HMGCR mRNA expression via quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR).

Main Results:

• Apigenin and luteolin reversed PMA-induced SREBP-2 protein processing in hepatic cells.
• Flavonoids attenuated PMA-induced SREBP-2 DNA-binding activity and nuclear SREBP-2 levels.
• Both flavones reduced HMGCR mRNA expression, with apigenin demonstrating a more potent effect.

Conclusions:

• Apigenin and luteolin inhibit SREBP-2 processing and subsequent HMGCR gene transcription via an AMPK-independent pathway.
• These findings suggest a potential role for these flavones in managing cholesterol metabolism.
• The study highlights the distinct inhibitory capacities of apigenin and luteolin on HMGCR expression.