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 i...

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Main Authors: Prasad P. Devarshi, Aarin D. Jones, Erin M. Taylor, Barbara Stefanska, Tara M. Henagan
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:PPAR Research
Online Access:http://dx.doi.org/10.1155/2017/3235693
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author Prasad P. Devarshi
Aarin D. Jones
Erin M. Taylor
Barbara Stefanska
Tara M. Henagan
author_facet Prasad P. Devarshi
Aarin D. Jones
Erin M. Taylor
Barbara Stefanska
Tara M. Henagan
author_sort Prasad P. Devarshi
collection DOAJ
description 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.
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spelling doaj-art-498bebd66bb843a6bdfb9519d921e3ab2025-08-20T03:36:48ZengWileyPPAR Research1687-47571687-47652017-01-01201710.1155/2017/32356933235693Quercetin and Quercetin-Rich Red Onion Extract Alter Pgc-1α Promoter Methylation and Splice Variant ExpressionPrasad P. Devarshi0Aarin D. Jones1Erin M. Taylor2Barbara Stefanska3Tara M. Henagan4Department of Nutrition Science, Purdue University, West Lafayette, IN, USADepartment of Nutrition Science, Purdue University, West Lafayette, IN, USADepartment of Nutrition Science, Purdue University, West Lafayette, IN, USADepartment of Nutrition Science, Purdue University, West Lafayette, IN, USADepartment of Nutrition Science, Purdue University, West Lafayette, IN, USAPgc-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.http://dx.doi.org/10.1155/2017/3235693
spellingShingle Prasad P. Devarshi
Aarin D. Jones
Erin M. Taylor
Barbara Stefanska
Tara M. Henagan
Quercetin and Quercetin-Rich Red Onion Extract Alter Pgc-1α Promoter Methylation and Splice Variant Expression
PPAR Research
title Quercetin and Quercetin-Rich Red Onion Extract Alter Pgc-1α Promoter Methylation and Splice Variant Expression
title_full Quercetin and Quercetin-Rich Red Onion Extract Alter Pgc-1α Promoter Methylation and Splice Variant Expression
title_fullStr Quercetin and Quercetin-Rich Red Onion Extract Alter Pgc-1α Promoter Methylation and Splice Variant Expression
title_full_unstemmed Quercetin and Quercetin-Rich Red Onion Extract Alter Pgc-1α Promoter Methylation and Splice Variant Expression
title_short Quercetin and Quercetin-Rich Red Onion Extract Alter Pgc-1α Promoter Methylation and Splice Variant Expression
title_sort quercetin and quercetin rich red onion extract alter pgc 1α promoter methylation and splice variant expression
url http://dx.doi.org/10.1155/2017/3235693
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