Dietary Fructose and GLUT5 Transporter Activity Contribute to Antipsychotic-Induced Weight Gain.
Dietary Fructose and GLUT5 Transporter Activity Contribute to Antipsychotic-Induced Weight Gain.
复制标题
膳食果糖和 GLUT5 转运蛋白活性有助于抗精神病药物引起的体重增加。
DOI：
10.1093/schbul/sbw037
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发表时间：
2016
影响因子：
6.6
通讯作者：
Kuzhikandathil,EldoV
中科院分区：
文献类型：
--
作者：
Palavicino-Maggio,CarolineB;Kuzhikandathil,EldoV
下丘脑中的抗精神病药物受体有助于抗精神病药物诱导的体重增加;然而，这些受体中的许多也在肠中表达。尚未在抗精神病药物诱导的体重增加的背景下研究这些脑内表达的受体的作用及其对营养吸收的潜在调节。在这里，我们测试了饮食果糖和肠道果糖摄取对氯氮平诱导的小鼠体重增加的影响。在野生型小鼠和缺乏GLUT 5果糖转运蛋白的小鼠中测定体重增加，这些小鼠“口服”20 mg/kg氯氮平28天。为了评估饮食中果糖的作用，给氯氮平处理的小鼠喂食含有不同水平果糖的受控饮食。氯氮平治疗对肠道果糖转运活性和各种受体的表达水平的影响，结合氯氮平，以及几个基因参与胚胎发育和脂肪生成，采用实时RT-PCR和蛋白质印迹法进行测量。口服氯氮平显著增加野生型C57 BL/6小鼠的体重，但在GLUT 5缺失小鼠中没有。氯氮平诱导的体重增加与饮食中果糖的百分比成正比。氯氮平治疗的小鼠增加了肠道果糖摄取，而不改变肠道GLUT 5的表达水平。氯氮平治疗的小鼠表达显着更高水平的肠H1组胺受体在野生型，但不是GLUT 5 null小鼠。氯氮平还增加了果糖激酶和几个基因在肠道中的表达，这些基因参与了脂肪生成和脂肪生成。我们的研究结果表明，增加肠道吸收和代谢的果糖有助于氯氮平诱导的体重增加。消除饮食中的果糖可能会防止抗精神病药物引起的体重增加。
Receptors for antipsychotics in the hypothalamus contribute to antipsychotics-induced weight gain; however, many of these receptors are also expressed in the intestine. The role of these intestinally-expressed receptors, and their potential modulation of nutrient absorption, have not been investigated in the context of antipsychotics-induced weight gain. Here we tested the effect of dietary fructose and intestinal fructose uptake on clozapine-induced weight gain in mice. Weight gain was determined in wild type mice and mice lacking the GLUT5 fructose transporter that were “orally-administered” 20mg/kg clozapine for 28 days. To assess the role of dietary fructose, clozapine-treated mice were fed controlled diets with different levels of fructose. Effect of clozapine treatment on intestinal fructose transport activity and expression levels of various receptors that bind clozapine, as well as several genes involved in gluconeogenesis and lipogenesis were measured using real-time RT-PCR and western blotting. Oral administration of clozapine significantly increased body weight in wild type C57BL/6 mice but not in GLUT5 null mice. The clozapine-induced weight gain was proportional to the percentage of fructose in the diet. Clozapine-treated mice increased intestinal fructose uptake without changing the intestinal expression level of GLUT5. Clozapine-treated mice expressed significantly higher levels of intestinal H1 histamine receptor in the wild type but not GLUT5 null mice. Clozapine also increased the intestinal expression of fructokinase and several genes involved in gluconeogenesis and lipogenesis. Our results suggest that increased intestinal absorption and metabolism of fructose contributes to clozapine-induced weight gain. Eliminating dietary fructose might prevent antipsychotics-induced weight gain.