2021年3月16日 · FoxO1 governs lipid accumulation in cardiomyocytes, and overexpression of Xbp1s triggers FoxO1 ubiquitination and proteasomal degradation. Using gain- and loss-of-function approaches we...

Hyperactivated IRE1α in the XBP1-deficient liver degrades the lipid metabolism-associated mRNAs involved in lipogenesis (Dgat2, Acacb, and Scd1) and lipoprotein metabolism (angiopoietin-like protein 3 (Angptl3) and carboxylesterase 1 (Ces1)). ANGPTL3 inhibits lipoprotein lipase and endothelial lipase, and CES1 has TG and cholesterol-ester ...

XBP1 decreased glucose dysfunction via funneling its effects on improving insulin sensitivity and stimulating insulin secretion. However, XBP1 also yields its double-edged effects, driving the transformation from excess glucose to lipid, which is a key contribution to obesity and T2DM.

2016年3月1日 · X-box binding protein 1 (XBP1) is a major, well-conserved component of the unfolded protein response (UPR) that is crucial for glucose homeostasis and lipid metabolism. Metabolic dysfunction has been associated with XBP1 transcriptional activity.

Imanikia et al. find that expressing the transcription factor xbp-1s in C. elegans remodels lipid metabolism, decreasing triglyceride and increasing oleic acid (OA) levels. Increased OA levels may involve the activity of lysosomal lipases and a Δ9 desaturase, and are sufficient to increase lifespan and protect animals from proteotoxicity.

2004年10月11日 · Cells overexpressing XBP1 (S) exhibit elevated levels of membrane phospholipids, increased surface area and volume of rough ER, and enhanced activity of the cytidine diphosphocholine pathway of phosphatidylcholine biosynthesis. These data suggest that XBP1 (S) links the mammalian UPR to phospholipid biosynthesis and ER biogenesis.

2022年8月6日 · Recent studies showed that unspliced XBP1 (XBP1-u) has unique biological functions independent from XBP1-s and could promote tumorigenesis; however, whether it is involved in tumor metabolic reprogramming remains unknown. Herein, we found that XBP1-u promotes tumor growth by enhancing cholesterol biosynthesis in hepatocellular carcinoma (HCC ...

Genetic interaction and biochemical analyses revealed that Ire1 regulates lipid mobilization by promoting Xbp1s-associated FoxO degradation and suppressing FoxO-dependent lipolytic programs. Our results demonstrate that Ire1 is a catabolic sensor and acts through the Xbp1s-FoxO axis to hamper the lipolytic response during chronic food deprivation.

Cells overexpressing XBP1 (S) exhibit elevated levels of membrane phospholipids, increased surface area and volume of rough ER, and enhanced activity of the cytidine diphosphocholine pathway of phosphatidylcholine biosynthesis. These data suggest that XBP1 (S) links the mammalian UPR to phospholipid biosynthesis and ER biogenesis.

XBP1-u promotes HCC cholesterol biosynthesis. To explore whether XBP1 was involved in lipid metabolism of tumor cells, we first silenced XBP1 in HCC-LM3, MHCC-97H, and HepG2 hepatocarcinoma cells using two shRNA expression vectors targeting XBP1 (Supplementary Fig. S1A) and examined its effect on lipid accumulation.