التفاصيل البيبلوغرافية
| العنوان: |
PPARα affects hepatic lipid homeostasis by perturbing necroptosis signals in the intestinal epithelium. |
| المؤلفون: |
Na, Shufang, Fan, Yanjie, Chen, HongLei, Li, Ling, Li, Guolin, Zhang, Furong, Wang, Rongyan, Yang, Yafei, Shen, Zixia, Peng, Zhuang, Wu, Yafei, Zhu, Yong, Yang, Zheqiong, Dong, Guicheng, Ye, Qifa, Yue, Jiang |
| المصدر: |
Acta Pharmaceutica Sinica B; Nov2024, Vol. 14 Issue 11, p4858-4873, 16p |
| مصطلحات موضوعية: |
INTESTINAL mucosa, INFLAMMATORY mediators, FATTY liver, HEPATIC fibrosis, SMALL intestine |
| مستخلص: |
Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPAR α is highly expressed in the small intestine and regulates the absorption of dietary lipids. However, as a key mediator of inflammation, the impact of intestinal PPAR α signaling on cell death pathways is unknown. Here, we show that Pparα deficiency of intestinal epithelium up-regulates necroptosis signals, disrupts the gut vascular barrier, and promotes LPS translocation into the liver. Intestinal Pparα deficiency drives age-related hepatic steatosis and aggravates hepatic fibrosis induced by a high-fat plus high-sucrose diet (HFHS). PPAR α levels correlate with TRIM38 and MLKL in the human ileum. Inhibition of PPAR α up-regulates necroptosis signals in the intestinal organoids triggered by TNF- α and LPS stimuli via TRIM38/TRIF and CREB3L3/MLKL pathways. Butyric acid ameliorates hepatic steatosis induced by intestinal Pparα deficiency through the inhibition of necroptosis. Our data suggest that intestinal PPAR α is essential for the maintenance of microenvironmental homeostasis and the spread of inflammation via the gut–liver axis. Pparα deficiency in the ileum epithelium up-regulates necroptosis signals via TRIM38/TRIF and CREB3L3/MLKL pathways, leading to hepatic steatosis through the spread of gut-derived endotoxin. [Display omitted] [ABSTRACT FROM AUTHOR] |
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