Nutritional strategy to prevent fatty liver and insulin resistance independent of obesity by reducing glucose-dependent insulinotropic polypeptide responses in mice
Nutritional strategy to prevent fatty liver and insulin resistance independent of obesity by reducing glucose-dependent insulinotropic polypeptide responses in mice
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DOI：
10.1007/s00125-014-3423-5
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发表时间：
2015-02-01
期刊：
影响因子：
8.2
通讯作者：
Pfeiffer, Andreas F. H.
中科院分区：
文献类型：
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作者：
Keyhani-Nejad, Farnaz;Irmler, Martin;Pfeiffer, Andreas F. H.
在西方社会，碳水化合物，特别是蔗糖的高摄入与非酒精性脂肪肝（NAFL）和糖尿病的发展有关。目前尚不清楚这是否主要与碳水化合物量或激素反应有关，特别是在近端肠道中释放的葡萄糖依赖性促胰岛素多肽（GIP）。因此，我们通过比较两种葡萄糖-果糖二聚体，蔗糖和帕拉金糖（异麦芽酮糖），近端或远端再吸收，研究GIP的作用。然后，我们分析了暴露于不同碳水化合物类型的等能饮食的C57 Bl/6 J小鼠的表型和代谢饮食诱导的变化。在GIP受体敲除（Gipr（-/-））小鼠及其野生型同窝小鼠中重复研究，与蔗糖相比，帕拉金糖摄入导致葡萄糖吸收较慢，餐后胰岛素和GIP水平降低。22周后，与蔗糖相比，帕拉金糖喂养可预防肝脂肪变性（48.5%），并改善葡萄糖耐量，而身体成分和食物摄入量无差异。Gipr（-/-）小鼠中GIP信号传导的消融完全防止了蔗糖喂养的有害代谢效应。此外，我们的微阵列分析表明，蔗糖增加了2.3倍的肝脏表达的Socs 2，这是参与生长激素信号通路，并参与NAFL.Our结果表明，葡萄糖吸收和GIP响应的网站决定肝脏脂肪积累和胰岛素抵抗的发展。GIP可能通过调节Socs 2的表达在蔗糖诱导的脂肪肝中发挥作用。
High intake of carbohydrates, particularly sucrose, in western societies is associated with the development of non-alcoholic fatty liver (NAFL) and diabetes mellitus. It is unclear whether this is related primarily to the carbohydrate quantity or to the hormonal responses, particularly glucose-dependent insulinotropic polypeptide (GIP), which is released in the proximal intestine. Therefore, we investigated the role of GIP by comparing two glucose-fructose dimers, sucrose and Palatinose (isomaltulose), resorbed proximally or distally.The glycaemic and incretin responses to sucrose and Palatinose were studied by oral gavage and meal tests. We then analysed phenotypic and metabolic diet-induced changes in C57Bl/6J mice exposed to isoenergetic diets differing in carbohydrate type. Studies were repeated in GIP receptor knockout (Gipr (-/-)) mice and their wild-type littermates.Compared with sucrose, Palatinose intake resulted in slower glucose absorption and reduced postprandial insulin and GIP levels. After 22 weeks, Palatinose feeding prevented hepatic steatosis (48.5%) compared with sucrose and improved glucose tolerance, without differences in body composition and food intake. Ablation of GIP signalling in Gipr (-/-) mice completely prevented the deleterious metabolic effects of sucrose feeding. Furthermore, our microarray analysis indicated that sucrose increased 2.3-fold the hepatic expression of Socs2, which is involved in the growth hormone signalling pathway and participates in the development of NAFL.Our results suggest that the site of glucose absorption and the GIP response determine liver fat accumulation and insulin resistance. GIP may play a role in sucrose induced fatty liver by regulating the expression of Socs2.