Increased consumption of fats and added sugars has been associated with an increase in metabolic syndromes. Here we show that mice chronically fed an energy-rich diet (ERD) with high fat and moderate sucrose have enhanced the absorption of a gastrointestinal fructose load, and this required expression of the arrestin domain protein Txnip in the intestinal epithelial cells. ERD feeding induced gene and protein expression of Glut5, and this required the expression of Txnip. Furthermore, Txnip interacted with Rab11a, a small GTPase that facilitates the apical localization of Glut5. We also demonstrate that ERD promoted Txnip/Glut5 complexes in the apical intestinal epithelial cell. Our findings demonstrate that ERD facilitates fructose absorption through a Txnip-dependent mechanism in the intestinal epithelial cell, suggesting that increased fructose absorption could potentially provide a mechanism for worsening of metabolic syndromes in the setting of a chronic ERD.

脂肪和添加糖消耗的增加与代谢综合征的增加有关。在这里，我们发现，长期喂食含有高脂肪和适量蔗糖的高能量饮食（ERD）的小鼠增强了胃肠道果糖负荷的吸收，这需要抑制蛋白结构域蛋白 Txnip 在肠上皮细胞中的表达。ERD 喂养诱导 Glut5 基因和蛋白表达，而这需要 Txnip 的表达。此外，Txnip 与 Rab11a 相互作用，Rab11a 是一种小型 GTP 酶，有助于 Glut5 的顶端定位。我们还证明 ERD 促进顶端肠上皮细胞中的 Txnip/Glut5 复合物。我们的研究结果表明，ERD 通过肠上皮细胞中的 Txnip 依赖性机制促进果糖吸收，这表明果糖吸收增加可能为慢性 ERD 情况下代谢综合征恶化提供一种机制。