Vitamin A and retinoic acid accelerate the attenuation of intestinal adaptability upon feeding induced by high-fat diet in mice
Vitamin A and retinoic acid accelerate the attenuation of intestinal adaptability upon feeding induced by high-fat diet in mice
复制标题
维生素A和视黄酸加速高脂饮食诱导小鼠肠道适应性减弱
DOI：
10.1016/j.jnutbio.2021.108803
复制
发表时间：
2021-07-12
影响因子：
5.6
通讯作者：
Li, Xiaobo
中科院分区：
文献类型：
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作者：
Hong, Wenting;Xu, Dongke;Li, Xiaobo
小肠粘膜以其独特的细胞可塑性，对摄食表现出有效的适应性。然而，关于高脂饮食（HFD）喂养对这种适应的影响及其潜在机制知之甚少。在本文中，我们证明了细胞增殖能力，线粒体形态和小肠的整体转录组学特征在小鼠禁食和再进食状态之间表现出显著差异，这些差异通过长期HFD喂养显著减弱。在小肠中，HFD喂养显著影响视黄醇（维生素A，VA）代谢途径。VA及其活性代谢产物维甲酸（RA）在给予脂质胶束的情况下，都促进了参与脂质吸收的基因的表达，并抑制了参与肠道类器官细胞增殖的基因的表达。通过chip-qPCR和RT-qPCR，参与脂质代谢和细胞增殖的基因是RA和脂质胶束处理的小肠类器官中RAR α/RXR α的靶基因。评价了VA在响应于HFD的肠适应性的体内衰减中的作用。给小鼠喂食正常饲料、HFD或补充有额外1.5倍VA的HFD饲料12周。高脂饮食中添加VA可加速高脂饮食诱导的肠道适应性衰减，促进脂质吸收基因表达，增加体重和血清胆固醇水平。因此，高脂饲料可显著降低禁食和再食状态下的小肠差异，VA和RA可能在其中起重要作用。(C)2021爱思唯尔公司All rights reserved.
With its unique cellular plasticity, the small intestinal mucosa exhibits efficient adaptability upon feeding. However, little is known about the effect of high-fat diet (HFD) feeding on this adaption and its underlying mechanism. Herein, we demonstrated that the cell proliferation ability, mitochondrial morphology, and global transcriptomic profile of the small intestine exhibited a prominent discrepancy between the fasted and refed state in mice, which were markedly attenuated by long-term HFD feeding. The retinol (Vitamin A, VA) metabolism pathway was dramatically affected by HFD feeding in the small intestine. Both VA and its active metabolite retinoic acid (RA), with the administration of lipid micelles, promoted the expression of genes involved in lipid absorption and suppressed the expression of genes involved in the cell proliferation of intestinal organoids. Via chip-qPCR and RT-qPCR, genes involved in lipid metabolism and cell proliferation were target genes of RAR alpha/RXR alpha in small intestinal organoids treated with RA and lipid micelles. The role of VA in the in vivo attenuation of intestinal adaptability, in response to HFD, was evaluated. Mice were fed a normal chow diet, HFD, or HFD diet supplemented with additional 1.5-fold VA for 12 weeks. VA supplementation in HFD accelerated the attenuation of intestinal adaptability upon feeding induced by HFD, promoted lipid absorption gene expression, and increased body weight and serum cholesterol levels. In conclusion, the discrepancy of the small intestine between the fasted and refed state was dramatically attenuated by HFD feeding, in which VA and RA might play important roles. (C) 2021 Elsevier Inc. All rights reserved.