Intestinal PPARδ protects against diet-induced obesity, insulin resistance and dyslipidemia.
Intestinal PPARδ protects against diet-induced obesity, insulin resistance and dyslipidemia.
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DOI：
10.1038/s41598-017-00889-z
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发表时间：
2017-04-12
影响因子：
4.6
通讯作者：
Jonker JW
中科院分区：
文献类型：
--
作者：
Doktorova M;Zwarts I;Zutphen TV;Dijk THV;Bloks VW;Harkema L;Bruin A;Downes M;Evans RM;Verkade HJ;Jonker JW
过氧化物酶体增殖物激活受体δ（Peroxisome proliferator-activated receptor δ，PPARδ）是一种配体激活的转录因子，在脂质代谢中起重要作用。在小鼠和人类中，激活PPARδ可刺激脂肪组织和骨骼肌中的脂肪酸氧化，并改善血脂异常。PPARδ在肠道中高度表达，但其在该器官中的生理功能尚不清楚。使用具有肠上皮细胞特异性缺失PPARδ的小鼠，我们表明肠PPARδ可防止饮食诱导的肥胖、胰岛素抵抗和血脂异常。此外，肠内PPARδ的缺乏消除了PPARδ激动剂GW 501516增加血浆HDL-胆固醇水平的能力。总之，我们的研究结果表明，肠道PPARδ在维持代谢稳态方面很重要，并表明，PPARδ的垂体特异性激活可能是治疗代谢综合征和血脂异常的一种治疗方法，同时避免全身毒性。
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.