Quercetin and Quercetin-Rich Red Onion Extract Alter Promoter Methylation and Splice Variant Expression.

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 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 isoform expression and DNA methylation were determined. Quantification of various isoforms, including isoforms , , , , total , and , showed that only total expression was increased in LF, HF + Q, and HF + RO compared to HF. Furthermore, Q supplementation decreased expression compared to LF and HF, and ROE decreased expression compared to LF. was decreased in HF + Q and HF + RO compared to LF and HF. HF exhibited hypermethylation at the -260 nucleotide (nt) in the promoter. Q and ROE prevented HFD-induced hypermethylation. -260 nt methylation levels were associated with expression only. isoform expression may be epigenetically regulated by Q and ROE through DNA methylation.