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

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. � 2017 prasad p. devarshi et al.