Rapamycin Inhibits Postprandial-Mediated X-Box-Binding Protein-1 Splicing in Rat Liver  

Oleh:

Pfaffenbach, Kyle T. ; Nivala, Angela M. ; Reese, Lauren

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: JN: The Journal of Nutrition vol. 140 no. 05 (May 2010), page 879-884.
Topik: RAPAMYCIN; ENDOPLASMIC RETICULUM (ER)

Ketersediaan

Perpustakaan FK Nomor Panggil: J42.K.2010.02 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

Recent studies have linked the unfolded protein response (UPR), in particular the inositol-requiring, endoplasmic reticulum-to-nucleus signaling protein 1{alpha} (IRE1{alpha})-X-box-binding protein-1 (XBP1) branch of the UPR, to the regulation of lipogenesis and hepatic steatosis. In this study, we examined the hypothesis that the postprandial environment can activate the IRE1{alpha}-XBP1 branch of the UPR in the liver via a mammalian target of rapamycin complex 1 (mTORC1)-dependent mechanism. Toward this end, rats were fed a high-carbohydrate diet (68% of energy from corn starch) for 3 h in the absence or presence of rapamycin (intraperitoneal injection of 1 mg/kg) and liver tissue was taken 1 or 7 h following the feeding period. Feeding activated the mTORC1 pathway and IRE1{alpha}, induced XBP1 splicing, and increased the expression of XBP1 target genes and lipogenic genes in the liver. The presence of rapamycin prevented the activation of mTORC1 and IRE1{alpha}, XBP1 splicing, and the increased expression of XBP1 target genes and lipogenic genes. Rapamycin also prevented the feeding-induced increase in nuclear sterol regulatory element binding protein 1c. These data suggest that the postprandial environment promotes activation of the IRE1-XBP1 branch of the UPR in the liver. This activation appears to be mediated in part by mTORC1.

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