Genetic defects in SAR1B GTPase inhibit chylomicron (CM) trafficking to the Golgi and result in a huge intraenterocyte lipid accumulation with a failure to release CMs and liposoluble vitamins into the blood circulation. The central aim of this study is to test the hypothesis that SAR1B deletion (SAR1B^-/- ) disturbs enterocyte lipid homeostasis (e.g., FA β-oxidation and lipogenesis) while promoting oxidative stress and inflammation. Another issue is to compare the impact of SAR1B^-/- to that of its paralogue SAR1A^-/- and combined SAR1A^-/- /B^-/- To address these critical issues, we have generated Caco-2/15 cells with a knockout of SAR1A, SAR1B, or SAR1A/B genes. SAR1B^-/- results in lipid homeostasis disruption, reflected by enhanced mitochondrial FA β-oxidation and diminished lipogenesis in intestinal absorptive cells via the implication of PPARα and PGC1α transcription factors. Additionally, SAR1B ^-/- cells, which mimicked enterocytes of CM retention disease, spontaneously disclosed inflammatory and oxidative characteristics via the implication of NF-κB and NRF2. In most conditions, SAR1A^-/- cells showed a similar trend, albeit less dramatic, but synergetic effects were observed with the combined defects of the two SAR1 paralogues. In conclusion, SAR1B and its paralogue are needed not only for CM trafficking but also for lipid homeostasis, prooxidant/antioxidant balance, and protection against inflammatory processes.

中文翻译：

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SAR1B GTPase对于保护肠道细胞免受脂质稳态，氧化应激和炎症的损害是必需的。

SAR1B GTPase的遗传缺陷抑制了乳糜微粒（CM）向高尔基体的运输，并导致巨大的肠内细胞脂质积聚，无法将CMs和脂溶性维生素释放到血液循环中。这项研究的主要目的是检验SAR1B缺失（SAR1B ^-/-）干扰肠细胞脂质稳态（例如FAβ氧化和脂肪生成），同时促进氧化应激和炎症的假说。另一个问题是将SAR1B ^-/-与其旁白SAR1A ^-/-和组合SAR1A ^-/- / B ^{-/-的影响进行比较}为了解决这些关键问题，我们已经产生了带有SAR1A，SAR1B或SAR1A / B基因敲除的Caco-2 / 15细胞。SAR1B ^-/-导致脂质体内稳态破坏，这通过增强线粒体FAβ氧化并通过吸收PPARα和PGC1α引起肠道吸收细胞的脂肪生成减少来反映。此外，模仿CM保留病肠细胞的SAR1B ^-/-细胞通过NF-κB和NRF2的表达自发地揭示了炎症和氧化特性。在大多数情况下，SAR1A ^-/- 细胞显示出相似的趋势，尽管不那么引人注目，但是在两个SAR1旁系同源蛋白的联合缺陷中观察到了协同作用。总之，SAR1B及其旁系同源物不仅对于CM转运是必需的，而且对于脂质稳态，促氧化剂/抗氧化剂的平衡以及对炎症过程的保护也是必需的。