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

• Published in: Scientific reports Vol. 7; no. 1; pp. 846 - 10
• Main Authors: Doktorova, Marcela, Zwarts, Irene, Zutphen, Tim van, Dijk, Theo H. van, Bloks, Vincent W., Harkema, Liesbeth, Bruin, Alain de, Downes, Michael, Evans, Ronald M., Verkade, Henkjan J., Jonker, Johan W.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.04.2017; Nature Portfolio
• Subjects: 38; 38/77; 631/443/319/1642/2037; 64; 64/60; 692/163/2743/2037; Animals; Cholesterol, HDL - blood; Dyslipidemias - genetics; Dyslipidemias - metabolism; Humanities and Social Sciences; Insulin Resistance; Intestinal Mucosa - metabolism; Mice; Mice, Inbred C57BL; multidisciplinary; Obesity - genetics; Obesity - metabolism; PPAR delta - agonists; PPAR delta - genetics; PPAR delta - metabolism; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-00889-z

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.