Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO 80045, USA.
Proc Natl Acad Sci U S A. 2012 Mar 13;109(11):4320-5. doi: 10.1073/pnas.1119908109. Epub 2012 Feb 27.
Fructose intake from added sugars correlates with the epidemic rise in obesity, metabolic syndrome, and nonalcoholic fatty liver disease. Fructose intake also causes features of metabolic syndrome in laboratory animals and humans. The first enzyme in fructose metabolism is fructokinase, which exists as two isoforms, A and C. Here we show that fructose-induced metabolic syndrome is prevented in mice lacking both isoforms but is exacerbated in mice lacking fructokinase A. Fructokinase C is expressed primarily in liver, intestine, and kidney and has high affinity for fructose, resulting in rapid metabolism and marked ATP depletion. In contrast, fructokinase A is widely distributed, has low affinity for fructose, and has less dramatic effects on ATP levels. By reducing the amount of fructose for metabolism in the liver, fructokinase A protects against fructokinase C-mediated metabolic syndrome. These studies provide insights into the mechanisms by which fructose causes obesity and metabolic syndrome.
果糖摄入与肥胖症、代谢综合征和非酒精性脂肪肝疾病的流行上升有关。果糖摄入还会导致实验动物和人类出现代谢综合征的特征。果糖代谢的第一酶是果糖激酶，它有两种同工酶形式，A 和 C。在这里，我们表明缺乏两种同工酶的小鼠可以预防果糖引起的代谢综合征，但缺乏果糖激酶 A 的小鼠则会加重代谢综合征。果糖激酶 C 主要在肝脏、肠道和肾脏中表达，对果糖具有高亲和力，导致快速代谢和显著的 ATP 耗竭。相比之下，果糖激酶 A 分布广泛，对果糖的亲和力低，对 ATP 水平的影响也不那么明显。通过减少肝脏中代谢果糖的量，果糖激酶 A 可预防果糖激酶 C 介导的代谢综合征。这些研究为果糖导致肥胖和代谢综合征的机制提供了新的见解。
