Quercetin and Quercetin-Rich Red Onion Extract AlterPgc-1αPromoter Methylation and Splice Variant Expression

Abstract

Pgc-1αand 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 upregulatingPgc-1αand 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 musclePgc-1αisoform expression and DNA methylation were determined. Quantification of variousPgc-1αisoforms, including isoformsPgc-1α-a,Pgc-1α-b,Pgc-1α-c,Pgc-1α4, totalNT-Pgc-1α, andFL-Pgc-1α, showed that only totalNT-Pgc-1αexpression was increased in LF, HF + Q, and HF + RO compared to HF. Furthermore, Q supplementation decreasedPgc-1α-aexpression compared to LF and HF, and ROE decreasedPgc-1α-aexpression compared to LF.FL-Pgc-1αwas decreased in HF + Q and HF + RO compared to LF and HF. HF exhibited hypermethylation at the −260 nucleotide (nt) in thePgc-1αpromoter. Q and ROE prevented HFD-induced hypermethylation. −260 nt methylation levels were associated withNT-Pgc-1αexpression only.Pgc-1αisoform expression may be epigenetically regulated by Q and ROE through DNA methylation.