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Sci Rep. 2017 Apr 12;7(1):846. doi: 10.1038/s41598-017-00889-z.

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

Author information

1
Section of Molecular Metabolism and Nutrition, Department of Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
2
Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
3
Dutch Molecular Pathology Center, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584, CL, Utrecht, The Netherlands.
4
Howard Hughes Medical Institute and Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California, 92037, USA.
5
Section of Molecular Metabolism and Nutrition, Department of Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. j.w.jonker@umcg.nl.

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.

PMID:
28404991
PMCID:
PMC5429805
DOI:
10.1038/s41598-017-00889-z
[Indexed for MEDLINE]
Free PMC Article

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