title: 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 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.
authors.affiliation: Section of Molecular Metabolism and Nutrition, Department of Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Marcela
authors.initials: M
authors.lastname: Doktorova
authors.affiliation: Section of Molecular Metabolism and Nutrition, Department of Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Irene
authors.initials: I
authors.lastname: Zwarts
authors.affiliation: Section of Molecular Metabolism and Nutrition, Department of Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Tim van
authors.initials: TV
authors.lastname: Zutphen
authors.affiliation: Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Theo H van
authors.initials: THV
authors.lastname: Dijk
authors.affiliation: Section of Molecular Metabolism and Nutrition, Department of Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Bloks
authors.affiliation: Dutch Molecular Pathology Center, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584, CL, Utrecht, The Netherlands.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Harkema
authors.affiliation: Section of Molecular Metabolism and Nutrition, Department of Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.|Dutch Molecular Pathology Center, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584, CL, Utrecht, The Netherlands.
authors.forename: Alain de
authors.initials: A
authors.lastname: Bruin
authors.affiliation: Howard Hughes Medical Institute and Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California, 92037, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Downes
authors.affiliation: Howard Hughes Medical Institute and Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California, 92037, USA.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Evans
authors.affiliation: Section of Molecular Metabolism and Nutrition, Department of Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Henkjan J
authors.initials: HJ
authors.lastname: Verkade
authors.affiliation: 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.
authors.forename: Johan W
authors.initials: JW
authors.lastname: Jonker
mesh_terms: D000818:Animals; D008076:Cholesterol, HDL / Q000097:blood; D050171:Dyslipidemias / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D047494:PPAR delta / Q000819:agonists / Q000235:genetics* / Q000378:metabolism
chemical_list: D008076:Cholesterol, HDL; D047494:PPAR delta