Intestinal PPARδ protects against diet-induced obesity, insulin resistance and dyslipidemia

Abstract Peroxisome proliferator-activated receptor δ (PPARδ) is a ligand-activated transcription factor that has an important role in lipid metabolism. Activation of PPARδ stimulates fatty acid oxidation in adipose tissue and skeletal muscle and improves dyslipidemia in mice and humans. PPARδ is hi...

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Autores principales:	Marcela Doktorova, Irene Zwarts, Tim van Zutphen, Theo H. van Dijk, Vincent W. Bloks, Liesbeth Harkema, Alain de Bruin, Michael Downes, Ronald M. Evans, Henkjan J. Verkade, Johan W. Jonker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/adc9aeb287f8410a912102df98040a2d
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spelling	oai:doaj.org-article:adc9aeb287f8410a912102df98040a2d2021-12-02T15:06:13ZIntestinal PPARδ protects against diet-induced obesity, insulin resistance and dyslipidemia10.1038/s41598-017-00889-z2045-2322https://doaj.org/article/adc9aeb287f8410a912102df98040a2d2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00889-zhttps://doaj.org/toc/2045-2322Abstract Peroxisome proliferator-activated receptor δ (PPARδ) is a ligand-activated transcription factor that has an important role in lipid metabolism. Activation of PPARδ stimulates fatty acid oxidation in adipose tissue and skeletal muscle and improves dyslipidemia in mice and humans. PPARδ is highly expressed in the intestinal tract but its physiological function in this organ is not known. Using mice with an intestinal epithelial cell-specific deletion of PPARδ, we show that intestinal PPARδ protects against diet-induced obesity, insulin resistance and dyslipidemia. Furthermore, absence of intestinal PPARδ abolished the ability of PPARδ agonist GW501516 to increase plasma levels of HDL-cholesterol. Together, our findings show that intestinal PPARδ is important in maintaining metabolic homeostasis and suggest that intestinal-specific activation of PPARδ could be a therapeutic approach for treatment of the metabolic syndrome and dyslipidemia, while avoiding systemic toxicity.Marcela DoktorovaIrene ZwartsTim van ZutphenTheo H. van DijkVincent W. BloksLiesbeth HarkemaAlain de BruinMichael DownesRonald M. EvansHenkjan J. VerkadeJohan W. JonkerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marcela Doktorova Irene Zwarts Tim van Zutphen Theo H. van Dijk Vincent W. Bloks Liesbeth Harkema Alain de Bruin Michael Downes Ronald M. Evans Henkjan J. Verkade Johan W. Jonker Intestinal PPARδ protects against diet-induced obesity, insulin resistance and dyslipidemia
description	Abstract Peroxisome proliferator-activated receptor δ (PPARδ) is a ligand-activated transcription factor that has an important role in lipid metabolism. Activation of PPARδ stimulates fatty acid oxidation in adipose tissue and skeletal muscle and improves dyslipidemia in mice and humans. PPARδ is highly expressed in the intestinal tract but its physiological function in this organ is not known. Using mice with an intestinal epithelial cell-specific deletion of PPARδ, we show that intestinal PPARδ protects against diet-induced obesity, insulin resistance and dyslipidemia. Furthermore, absence of intestinal PPARδ abolished the ability of PPARδ agonist GW501516 to increase plasma levels of HDL-cholesterol. Together, our findings show that intestinal PPARδ is important in maintaining metabolic homeostasis and suggest that intestinal-specific activation of PPARδ could be a therapeutic approach for treatment of the metabolic syndrome and dyslipidemia, while avoiding systemic toxicity.
format	article
author	Marcela Doktorova Irene Zwarts Tim van Zutphen Theo H. van Dijk Vincent W. Bloks Liesbeth Harkema Alain de Bruin Michael Downes Ronald M. Evans Henkjan J. Verkade Johan W. Jonker
author_facet	Marcela Doktorova Irene Zwarts Tim van Zutphen Theo H. van Dijk Vincent W. Bloks Liesbeth Harkema Alain de Bruin Michael Downes Ronald M. Evans Henkjan J. Verkade Johan W. Jonker
author_sort	Marcela Doktorova
title	Intestinal PPARδ protects against diet-induced obesity, insulin resistance and dyslipidemia
title_short	Intestinal PPARδ protects against diet-induced obesity, insulin resistance and dyslipidemia
title_full	Intestinal PPARδ protects against diet-induced obesity, insulin resistance and dyslipidemia
title_fullStr	Intestinal PPARδ protects against diet-induced obesity, insulin resistance and dyslipidemia
title_full_unstemmed	Intestinal PPARδ protects against diet-induced obesity, insulin resistance and dyslipidemia
title_sort	intestinal pparδ protects against diet-induced obesity, insulin resistance and dyslipidemia
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/adc9aeb287f8410a912102df98040a2d
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Intestinal PPARδ protects against diet-induced obesity, insulin resistance and dyslipidemia

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