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

Abstract EN

Pgc-1α and its various isoforms may play a role in determining skeletal muscle mitochondrial adaptations in response to diet.

8 wks of dietary supplementation with the flavonoid quercetin (Q) or red onion extract (ROE) in a high fat diet (HFD) ameliorates HFD-induced obesity and insulin resistance in C57BL/J mice while upregulating Pgc-1α and increasing skeletal muscle mitochondrial number and function.

Here, mice were fed a low fat (LF), high fat (HF), high fat plus quercetin (HF + Q), or high fat plus red onion extract (HF + RO) diet for 9 wks and skeletal muscle Pgc-1α isoform expression and DNA methylation were determined.

Quantification of various Pgc-1α isoforms, including isoforms Pgc-1α-a, Pgc-1α-b, Pgc-1α-c, Pgc-1α4, total NT-Pgc-1α, and FL-Pgc-1α, showed that only total NT-Pgc-1α expression was increased in LF, HF + Q, and HF + RO compared to HF.

Furthermore, Q supplementation decreased Pgc-1α-a expression compared to LF and HF, and ROE decreased Pgc-1α-a expression compared to LF.

FL-Pgc-1α was decreased in HF + Q and HF + RO compared to LF and HF.

HF exhibited hypermethylation at the −260 nucleotide (nt) in the Pgc-1α promoter.

Q and ROE prevented HFD-induced hypermethylation.

−260 nt methylation levels were associated with NT-Pgc-1α expression only.

Pgc-1α isoform expression may be epigenetically regulated by Q and ROE through DNA methylation.