果糖代谢只在肝脏细胞完成一直是我的旧认知，最近刚看到一篇2018年发表在Cell Metabolism的论文如下链接。
https://www.sciencedirect.com/science/article/pii/S1550413117307295?via%3Dihub
这篇论文的主旨是，低剂量摄入的果糖 90% 可以被小肠吸收而不会到达肝脏，高剂量果糖摄入（>=1g/kg）会使小肠吸收饱和而到达肝脏。
他们的研究方法是使用同位素标记测定portal vein（连接小肠与肝脏）中果糖1磷酸的量。后续也做了敲除Khk基因来确认。
下面的这个图C显示很清楚。
这个是Portal blood里面的代谢标记，分别做了Khk KO/WT
一般的结论就是低剂量果糖不太可能对肝脏造成负担，更不会伤害。
关于Limitation的讨论不长，也附在此。关于对于人体发生作用的Dose部分在最后做了开放式讨论：
Study Limitations
There is substantial epidemiological and experimental evidence linking fructose consumption to metabolic disease, especially fatty liver. The link between fructose and metabolic disease, however, remains controversial (van Buul et al., 2014; Caliceti et al., 2017; Jegatheesan and De Bandt, 2017). Nothing in the present manuscript addresses whether fructose is more toxic than other sugars or carbohydrates.
We do, however, definitively determine the main site of dietary fructose clearance in mice: the small intestine. Because higher doses of fructose overwhelm the small intestine and spill over to the liver, it is tempting to speculate that fructose metabolism in the small intestine is safe (physiologic), whereas fructose metabolism in the liver drives metabolic disease (pathologic, at least for individuals with consistent access to abundant high-calorie foods). We do not, however, test this hypothesis. Indeed, it is possible that intestinal metabolism of fructose drives metabolic disease.
Another important limitation regards the dose response to fructose. In fasted mice, there is a shift toward greater hepatic fructose metabolism between 0.25 g/kg and 1 g/kg fructose gavage. We consider it likely that this basic trend is conserved across many mammals—lower doses of fructose are cleared by the intestine and higher doses spill over to liver—but our current data are limited to C57BL/6 mice. Moreover, even if the basic trend is conserved, the dose response may vary. Understanding the associated dose-response pattern in humans is of critical importance, but not addressed experimentally here.
我有一点疑问就是Ketohexokinase如何在肝脏外表达，如果可以得到一些解惑或者提示会非常非常感谢。
我很少参加耐力运动，为了提高体能有一些长跑训练，最多不超过10公里。我自己喜欢的运动大半都是无氧代谢，碳水代谢多，所以很想弄明白。
非常感谢！
