Positive regulatory control loop between gut leptin and intestinal GLUT2/GLUT5 transporters links to hepatic metabolic functions in rodents.
Positive regulatory control loop between gut leptin and intestinal GLUT2/GLUT5 transporters links to hepatic metabolic functions in rodents.
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DOI：
10.1371/journal.pone.0007935
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发表时间：
2009-11-30
期刊：
影响因子：
3.7
通讯作者：
Bado A
中科院分区：
文献类型：
--
作者：
Sakar Y;Nazaret C;Lettéron P;Ait Omar A;Avenati M;Viollet B;Ducroc R;Bado A
小肠是吸收膳食糖的主要场所。它们进入和离开肠道的速度对血糖稳态有重大影响。在这项研究中，我们确定了管腔瘦素对 GLUT2 和 GLUT5 转运蛋白响应糖摄入的活性/表达的影响，并分析了它们的生理后果。使用Wistar大鼠、野生型和AMPKα2-/-小鼠。体外和体内分离的空肠环用于量化在瘦素不存在和存在的情况下果糖和半乳糖的转运。测定了果糖和半乳糖对胃瘦素释放的影响。测定了口服瘦素（不含或含有果糖）对 GLUT2/5 表达、肠和肝脏中一些糖异生和脂肪生成酶的影响。首先，体外管腔瘦素激活其与 PKCβII 和 AMPKα 偶联的受体，增加 GLUT2/5 插入刷状缘膜，从而增强半乳糖和果糖转运。其次，在体内，口服果糖而非半乳糖诱导小鼠在胃液中快速有效地释放胃瘦素，而血浆瘦素水平没有显着变化。此外，口服瘦素的剂量可产生与果糖诱导的水平相当的水平，刺激 GLUT5-果糖转运，并增强果糖诱导的：i) 血糖和关键糖异生酶的 mRNA 水平增加； ii) 血液甘油三酯增加，肠和肝禁食诱导脂肪细胞因子 (Fiaf) mRNA 水平降低，以及 iii) 肝脏中 SREBP-1c、ACC-1、FAS mRNA 水平增加以及 ACC-1 去磷酸化/激活。这些数据首次确定了肠道瘦素和果糖之间的正向调节控制环，其中果糖触发胃瘦素的释放，进而上调 GLUT5 并同时调节肝脏的代谢功能。这种循环似乎是一种新机制（可能是致病性的），通过该机制，果糖的消耗会迅速变得高度脂肪生成和有害。
The small intestine is the major site of absorption of dietary sugars. The rate at which they enter and exit the intestine has a major effect on blood glucose homeostasis. In this study, we determine the effects of luminal leptin on activity/expression of GLUT2 and GLUT5 transporters in response to sugars intake and analyse their physiological consequences. Wistar rats, wild type and AMPKα2 −/− mice were used. In vitro and in vivo isolated jejunal loops were used to quantify transport of fructose and galactose in the absence and the presence of leptin. The effects of fructose and galactose on gastric leptin release were determined. The effects of leptin given orally without or with fructose were determined on the expression of GLUT2/5, on some gluconeogenesis and lipogenic enzymes in the intestine and the liver. First, in vitro luminal leptin activating its receptors coupled to PKCβII and AMPKα, increased insertion of GLUT2/5 into the brush-border membrane leading to enhanced galactose and fructose transport. Second in vivo, oral fructose but not galactose induced in mice a rapid and potent release of gastric leptin in gastric juice without significant changes in plasma leptin levels. Moreover, leptin given orally at a dose reproducing comparable levels to those induced by fructose, stimulated GLUT5-fructose transport, and potentiated fructose-induced: i) increase in blood glucose and mRNA levels of key gluconeogenesis enzymes; ii) increase in blood triglycerides and reduction of mRNA levels of intestinal and hepatic Fasting-induced adipocyte factor (Fiaf) and iii) increase in SREBP-1c, ACC-1, FAS mRNA levels and dephosphorylation/activation of ACC-1 in liver. These data identify for the first time a positive regulatory control loop between gut leptin and fructose in which fructose triggers release of gastric leptin which, in turn, up-regulates GLUT5 and concurrently modulates metabolic functions in the liver. This loop appears to be a new mechanism (possibly pathogenic) by which fructose consumption rapidly becomes highly lipogenic and deleterious.
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DOI：
10.1073/pnas.0809255105
发表时间：
2008-11-04
影响因子：
11.1
作者：
Cha, Seung Hun;Wolfgang, Michael;Lane, M. Daniel
通讯作者：
Lane, M. Daniel
影响因子：
4.8
作者：
Barone, Sharon;Fussell, Stacey L.;Soleimani, Manoocher
通讯作者：
Soleimani, Manoocher
DOI：
10.1152/ajpgi.00334.2005
发表时间：
2006-02-01
影响因子：
4.5
作者：
Cammisotto, PG;Gingras, D;Bendayan, M
通讯作者：
Bendayan, M
DOI：
10.1073/pnas.96.22.12737
发表时间：
1999-10-26
影响因子：
11.1
作者：
Foretz, M;Guichard, C;Foufelle, F
通讯作者：
Foufelle, F
影响因子：
4.1
作者：
Au, A;Gupta, A;Cheeseman, CI
通讯作者：
Cheeseman, CI