我曾在 喝水或饮料减肥靠谱吗？ 一文中介绍， 前两天Science Daily网站刚刚报道：佐餐饮料对减肥有益（ http://www.sciencedaily.com/releases/2014/05/140527085124.htm ）！可是，昨天同一网站却说超重及肥胖儿童应少喝含糖饮料（ http://www.sciencedaily.com/releases/2014/06/140603161938.htm ）！前一项研究结果发表在权威的Obesity杂志上，后一项结果发表在著名的J Biol Chem杂志上。 为何两项研究获得的结论截然相反？经过仔细比较发现，第一项研究中所用的佐餐饮料是苏打、汽水和茶，而第二项研究中所用的却是含糖饮料（如甜玉米高果糖浆）。因此，两者最大的区别是一个不含果糖，而另一个含有果糖！也就是说，这两项研究的结论并不矛盾。 这项研究发现，果糖对肥胖似乎没有直接影响，但它能促使肝脏贮存脂肪，从而诱发 非酒精性脂肪肝（NAFLD）。果糖 之所以会成为脂肪肝的“罪魁祸首”，是因为它通过肝细胞表面的果糖-葡萄糖双特异性转运蛋白GLUT8运进肝细胞后，可以转变成甘油三酯贮存起来。假如利用基因敲除技术阻断GLUT8的运载功能，那么果糖就无法进入肝细胞，也就不能转变成脂肪而引起脂肪肝了。不过，果糖转变成脂肪贮存在周围组织中 仍能导致全身性代谢综合征。 有趣的是，将 GLUT8的功能阻断后，在雌鼠与雄鼠中观察到不同的结果：饲喂高果糖饮食的雄鼠仍会形成脂肪肝，但无全身性代谢综合征；相反，饲喂果糖的雌鼠的肝脏看起来似乎很健康，但却会出现全身性代谢综合征。原来，无 GLUT8的 雌鼠将果糖来源的脂肪堆积在皮下脂肪组织中，其血中的甘油三酯及胆固醇含量均超标。 由于人与小鼠的果糖运输及代谢机理相同，因此 根据这个研究结果可知， 喝高浓度果糖饮料很危险，而喝无糖饮料较安全。不过，水果中含有大量果糖，莫非经常食用水果也能引起脂肪肝？对此，目前还不清楚，有兴趣者可以做做追踪研究。 个人感觉，这项研究有点“见树不见林”！比如，它只考虑了果糖与GLUT8之间的相互关系，而没有考虑其他单糖尤其是葡萄糖与相应运输蛋白之间的作用及其后果。理论上，任何单糖都可以在体内转变成脂类（包括甘油三酯和胆固醇）贮存，而并非只有果糖才是肝细胞内贮脂的唯一来源。因此，这篇文章的研究结果仅仅涉及葡萄糖以外的果糖对脂肪肝形成的影响。 过去的流行病学证据早已证实，过量摄入富含碳水化合物的食物将触发肝细胞内脂肪积累，而这种现象也已在啮齿类动物中被发现。然而，脂肪肝的诱发因素绝不仅仅限于果糖的超量摄取，其他高危因素还包括：高脂饮食、游离脂肪酸运进肝细胞、肝细胞内脂质从头合成、脂肪酸运出肝细胞障碍和脂肪酸β-氧化障碍等。 现在所有研究脂肪肝的人，都忽略了几个关键问题：既然脂肪对肝细胞没有好处，为什么肝细胞要把摄入的单糖转变成脂肪？又是什么因素让肝细胞把单糖转变成肝脂肪而不是肝糖原？肝炎和脂肪肝哪个是因，哪个是果？ 我们正在做肥胖与脂肪肝相关性研究，我们提出一个假说：先有肝炎，后才有脂肪肝。我们推测，肝细胞为了清除病原体感染，需要激活大量免疫细胞，而免疫细胞的杀伤作用则要消耗大量能量，于是肝细胞便将摄入的单糖转变成脂肪。 若该假说得到实验证实，就能说明预防脂肪肝的关键仍然是抗感染导致的肝炎，而且可以解释脂肪为何会在内脏积累，还将从侧面印证“肥胖不是病”的理念，因为只有当内脏发生炎症后，脂肪才会贮存在内脏（致病），而通常脂肪将贮存在皮下脂肪组织（不致病）。 以下是Science Daily报道全文，链接为： http://www.sciencedaily.com/releases/2014/06/140603161938.htm Fatty liver disease prevented in mice Date: June 3, 2014 Source: Washington University in St. Louis Summary: Studying mice, researchers have found a way to prevent nonalcoholic fatty liver disease, the most common cause of chronic liver disease worldwide. Blocking a path that delivers dietary fructose to the liver prevented mice from developing the condition, according to investigators. A transporter called GLUT8 (green) is in the outer membrane of liver cells. In mice, blocking GLUT8 stops fructose from entering the liver and protects against nonalcoholic fatty liver disease. The liver cell nuclei are shown in blue. Credit: Brian J. DeBosch Studying mice, researchers have found a way to prevent nonalcoholic fatty liver disease, the most common cause of chronic liver disease worldwide. Blocking a path that delivers dietary fructose to the liver prevented mice from developing the condition, according to investigators at Washington University School of Medicine in St. Louis. The study appears in a recent issue of The Journal of Biological Chemistry . In people, nonalcoholic fatty liver disease often accompanies obesity, elevated blood sugar, high blood pressure and other markers of metabolic syndrome. Some estimate as many as 1 billion people worldwide have fatty liver disease, though some may not realize it. Fatty liver disease is a major topic of research right now, said first author Brian J. DeBosch, MD, PhD, clinical fellow in pediatric gastroenterology. There are competing hypotheses about the origins of metabolic syndrome. One of these hypotheses is that insulin resistance begins to develop in the liver first. The thought is if we can prevent the liver from becoming unhealthy to begin with, maybe we can block the entire process from moving forward. The research team, led by Kelle H. Moley, MD, the James P. Crane Professor of Obstetrics and Gynecology, showed that a molecule called GLUT8 carries large amounts of fructose into liver cells. Fructose is a type of sugar found in many foods. It is present naturally in fruit and is added to soft drinks and myriad other products in the form of high-fructose corn syrup. Scientists have known that fructose is processed in the liver and stored there as fat in the form of triglycerides. In this study, researchers showed that blocking or eliminating GLUT8 in mice reduced the amount of fructose entering the organ and appeared to prevent the development of fatty livers. Mice with GLUT8 deficiency also appeared to burn liver fat at a faster rate than control mice. We showed that GLUT8 is required for fructose to get into the liver, DeBosch said. If you take away or block this transporter in mice, they no longer get diet-induced fatty liver disease. The researchers also saw differences between male and female mice in the degree to which they were protected from fatty livers and in whole-body metabolism. Male mice fed a high-fructose diet while deficient in GLUT8 still had evidence of fatty liver disease, but whole-body metabolism was healthy. They showed no evidence of metabolic syndrome in the rest of the body. Females fed fructose while lacking GLUT8, in contrast, had healthy looking livers but exhibited more evidence of whole-body metabolic syndrome. If the fructose doesn't go into the liver, it may go to peripheral tissues, DeBosch said. Female mice with a GLUT8 deficiency had increased body fat. They also had increased circulating triglycerides and cholesterol. So the liver is healthier in female rodents, but you could argue that the whole body has worse overall metabolic syndrome, he said. This supports the idea of the liver acting as a sort of sink for processing fructose. The liver protects the whole body, but it may do so at its own expense. While DeBosch said future therapeutics might be able to target GLUT8 to block fructose from entering the liver, more work must be done to understand how this would impact the rest of the body. In a perfect world, it would be good if we could figure out a way to direct fructose to tissues in which you're more likely to burn it than store it, such as in skeletal muscle, he said. In the meantime, DeBosch advises his pediatric patients, many of whom are overweight or obese, to avoid fructose, especially sugar-sweetened drinks, and to find ways to increase physical activity. Story Source: The above story is based on materials provided by Washington University in St. Louis . The original article was written by Julia Evangelou Strait. Note: Materials may be edited for content and length. Journal Reference : B. J. DeBosch, Z. Chen, J. L. Saben, B. N. Finck, K. H. Moley. Glucose Transporter 8 (GLUT8) Mediates Fructose-induced de Novo Lipogenesis and Macrosteatosis . Journal of Biological Chemistry , 2014; 289 (16): 10989 DOI: 10.1074/jbc.M113.527002
标签: 果糖
