Koo Hyun-Young, Wallig Matthew A, Chung Byung Hong, Nara Takayuki Y, Cho B H Simon, Nakamura Manabu T
Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 905 S. Goodwin Avenue, Urbana, IL 61801, USA.
Biochim Biophys Acta. 2008 May;1782(5):341-8. doi: 10.1016/j.bbadis.2008.02.007. Epub 2008 Feb 29.
Dietary fructose has been suspected to contribute to development of metabolic syndrome. However, underlying mechanisms of fructose effects are not well characterized. We investigated metabolic outcomes and hepatic expression of key regulatory genes upon fructose feeding under well defined conditions. Rats were fed a 63% (w/w) glucose or fructose diet for 4 h/day for 2 weeks, and were killed after feeding or 24-hour fasting. Liver glycogen was higher in the fructose-fed rats, indicating robust conversion of fructose to glycogen through gluconeogenesis despite simultaneous induction of genes for de novo lipogenesis and increased liver triglycerides. Fructose feeding increased mRNA of previously unidentified genes involved in macronutrient metabolism including fructokinase, aldolase B, phosphofructokinase-1, fructose-1,6-bisphosphatase and carbohydrate response element binding protein (ChREBP). Activity of glucose-6-phosphate dehydrogenase, a key enzyme for ChREBP activation, remained elevated in both fed and fasted fructose groups. In the fasted liver, the fructose group showed lower non-esterified fatty acids, triglycerides and microsomal triglyceride transfer protein mRNA, suggesting low VLDL synthesis even though plasma VLDL triglycerides were higher. In conclusion, fructose feeding induced a broader range of genes than previously identified with simultaneous increase in glycogen and triglycerides in liver. The induction may be in part mediated by ChREBP.
膳食果糖一直被怀疑与代谢综合征的发生有关。然而，果糖作用的潜在机制尚未得到充分阐明。我们在明确的条件下研究了果糖喂养后大鼠的代谢结果以及关键调控基因的肝脏表达情况。大鼠分别喂食63%（w/w）的葡萄糖或果糖饮食，每天4小时，持续2周，喂食后或禁食24小时后处死。果糖喂养组大鼠的肝糖原含量更高，这表明尽管同时诱导了从头脂肪生成相关基因且肝脏甘油三酯增加，但果糖仍通过糖异生大量转化为糖原。果糖喂养增加了先前未被鉴定的参与大量营养素代谢的基因的mRNA表达，包括果糖激酶、醛缩酶B、磷酸果糖激酶-1、果糖-1,6-二磷酸酶和碳水化合物反应元件结合蛋白（ChREBP）。葡萄糖-6-磷酸脱氢酶是ChREBP激活的关键酶，其活性在喂食和禁食的果糖组中均保持升高。在禁食的肝脏中，果糖组的非酯化脂肪酸、甘油三酯和微粒体甘油三酯转移蛋白mRNA水平较低，这表明尽管血浆极低密度脂蛋白甘油三酯较高，但极低密度脂蛋白合成较低。总之，果糖喂养诱导的基因范围比先前发现的更广，同时肝脏中的糖原和甘油三酯增加。这种诱导可能部分由ChREBP介导。
