Hyper- and hypo- nutrition studies of the hepatic transcriptome and epigenome suggest that PPARα regulates anaerobic glycolysis

Abstract Diet plays a crucial role in shaping human health and disease. Diets promoting obesity and insulin resistance can lead to severe metabolic diseases, while calorie-restricted (CR) diets can improve health and extend lifespan. In this work, we fed mice either a chow diet (CD), a 16 week high-...

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Autores principales:	Anthony R. Soltis, Shmulik Motola, Santiago Vernia, Christopher W. Ng, Norman J. Kennedy, Simona Dalin, Bryan J. Matthews, Roger J. Davis, Ernest Fraenkel
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0ab74bf51b5343838089e195486e12c5
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spelling	oai:doaj.org-article:0ab74bf51b5343838089e195486e12c52021-12-02T15:05:44ZHyper- and hypo- nutrition studies of the hepatic transcriptome and epigenome suggest that PPARα regulates anaerobic glycolysis10.1038/s41598-017-00267-92045-2322https://doaj.org/article/0ab74bf51b5343838089e195486e12c52017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00267-9https://doaj.org/toc/2045-2322Abstract Diet plays a crucial role in shaping human health and disease. Diets promoting obesity and insulin resistance can lead to severe metabolic diseases, while calorie-restricted (CR) diets can improve health and extend lifespan. In this work, we fed mice either a chow diet (CD), a 16 week high-fat diet (HFD), or a CR diet to compare and contrast the effects of these diets on mouse liver biology. We collected transcriptomic and epigenomic datasets from these mice using RNA-Seq and DNase-Seq. We found that both CR and HFD induce extensive transcriptional changes, in some cases altering the same genes in the same direction. We used our epigenomic data to infer transcriptional regulatory proteins bound near these genes that likely influence their expression levels. In particular, we found evidence for critical roles played by PPARα and RXRα. We used ChIP-Seq to profile the binding locations for these factors in HFD and CR livers. We found extensive binding of PPARα near genes involved in glycolysis/gluconeogenesis and uncovered a role for this factor in regulating anaerobic glycolysis. Overall, we generated extensive transcriptional and epigenomic datasets from livers of mice fed these diets and uncovered new functions and gene targets for PPARα.Anthony R. SoltisShmulik MotolaSantiago VerniaChristopher W. NgNorman J. KennedySimona DalinBryan J. MatthewsRoger J. DavisErnest FraenkelNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anthony R. Soltis Shmulik Motola Santiago Vernia Christopher W. Ng Norman J. Kennedy Simona Dalin Bryan J. Matthews Roger J. Davis Ernest Fraenkel Hyper- and hypo- nutrition studies of the hepatic transcriptome and epigenome suggest that PPARα regulates anaerobic glycolysis
description	Abstract Diet plays a crucial role in shaping human health and disease. Diets promoting obesity and insulin resistance can lead to severe metabolic diseases, while calorie-restricted (CR) diets can improve health and extend lifespan. In this work, we fed mice either a chow diet (CD), a 16 week high-fat diet (HFD), or a CR diet to compare and contrast the effects of these diets on mouse liver biology. We collected transcriptomic and epigenomic datasets from these mice using RNA-Seq and DNase-Seq. We found that both CR and HFD induce extensive transcriptional changes, in some cases altering the same genes in the same direction. We used our epigenomic data to infer transcriptional regulatory proteins bound near these genes that likely influence their expression levels. In particular, we found evidence for critical roles played by PPARα and RXRα. We used ChIP-Seq to profile the binding locations for these factors in HFD and CR livers. We found extensive binding of PPARα near genes involved in glycolysis/gluconeogenesis and uncovered a role for this factor in regulating anaerobic glycolysis. Overall, we generated extensive transcriptional and epigenomic datasets from livers of mice fed these diets and uncovered new functions and gene targets for PPARα.
format	article
author	Anthony R. Soltis Shmulik Motola Santiago Vernia Christopher W. Ng Norman J. Kennedy Simona Dalin Bryan J. Matthews Roger J. Davis Ernest Fraenkel
author_facet	Anthony R. Soltis Shmulik Motola Santiago Vernia Christopher W. Ng Norman J. Kennedy Simona Dalin Bryan J. Matthews Roger J. Davis Ernest Fraenkel
author_sort	Anthony R. Soltis
title	Hyper- and hypo- nutrition studies of the hepatic transcriptome and epigenome suggest that PPARα regulates anaerobic glycolysis
title_short	Hyper- and hypo- nutrition studies of the hepatic transcriptome and epigenome suggest that PPARα regulates anaerobic glycolysis
title_full	Hyper- and hypo- nutrition studies of the hepatic transcriptome and epigenome suggest that PPARα regulates anaerobic glycolysis
title_fullStr	Hyper- and hypo- nutrition studies of the hepatic transcriptome and epigenome suggest that PPARα regulates anaerobic glycolysis
title_full_unstemmed	Hyper- and hypo- nutrition studies of the hepatic transcriptome and epigenome suggest that PPARα regulates anaerobic glycolysis
title_sort	hyper- and hypo- nutrition studies of the hepatic transcriptome and epigenome suggest that pparα regulates anaerobic glycolysis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0ab74bf51b5343838089e195486e12c5
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Hyper- and hypo- nutrition studies of the hepatic transcriptome and epigenome suggest that PPARα regulates anaerobic glycolysis

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