Quercetin and Quercetin-Rich Red Onion Extract Alter Pgc-1α Promoter Methylation and Splice Variant Expression

Area of Science:

• Metabolic Adaptations
• Mitochondrial Biology
• Nutritional Biochemistry

Background:

• Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α) influences skeletal muscle mitochondrial adaptations.
• Dietary interventions, including flavonoids like quercetin (Q) and red onion extract (ROE), may modulate these adaptations.
• High-fat diets (HFD) induce obesity and insulin resistance, impacting mitochondrial function.

Purpose of the Study:

• To investigate the effects of quercetin and red onion extract on Pgc-1α isoform expression and DNA methylation in skeletal muscle of mice fed a high-fat diet.
• To determine if these dietary supplements can ameliorate HFD-induced metabolic dysfunction by targeting Pgc-1α regulation.

Main Methods:

• Mice were fed low-fat (LF), high-fat (HF), HF + Q, or HF + RO diets for 9 weeks.
• Skeletal muscle Pgc-1α isoform expression (including Pgc-1α-a, -b, -c, -4, NT-Pgc-1α, FL-Pgc-1α) was quantified.
• DNA methylation at the Pgc-1α promoter (-260 nt) was analyzed.

Main Results:

• Total NT-Pgc-1α expression increased in LF, HF + Q, and HF + RO groups compared to HF.
• Quercetin and ROE supplementation reduced Pgc-1α-a expression.
• High-fat diet induced hypermethylation at the Pgc-1α promoter (-260 nt), which was prevented by Q and ROE.
• Methylation at -260 nt was associated only with NT-Pgc-1α expression.

Conclusions:

• Dietary quercetin and red onion extract can modulate Pgc-1α isoform expression in skeletal muscle.
• These compounds may prevent high-fat diet-induced epigenetic changes in the Pgc-1α promoter via DNA methylation.
• Pgc-1α isoform expression appears to be epigenetically regulated by quercetin and red onion extract through DNA methylation.