Laboratory of Renal Physiopathology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Am J Physiol Renal Physiol. 2013 Mar 15;304(6):F727-36. doi: 10.1152/ajprenal.00485.2012. Epub 2013 Jan 9.
Fructose in sweetened beverages (SB) increases the risk for metabolic and cardiorenal disorders, and these effects are in part mediated by a secondary increment in uric acid (UA). Rodents have an active uricase, thus requiring large doses of fructose to increase plasma UA and to induce metabolic syndrome and renal hemodynamic changes. We therefore hypothesized that the effects of fructose in rats might be enhanced in the setting of uricase inhibition. Four groups of male Sprague-Dawley rats (n = 7/group) were studied during 8 wk: water + vehicle (V), water + oxonic acid (OA; 750 mg/k BW), sweetened beverage (SB; 11% fructose-glucose combination) + V, and SB + OA. Systemic blood pressure, plasma UA, triglycerides (TG), glucose and insulin, glomerular hemodynamics, renal structural damage, renal cortex and liver UA, TG, markers of oxidative stress, mitDNA, fructokinase, and fatty liver synthase protein expressions were evaluated at the end of the experiment. Chronic hyperuricemia and SB induced features of the metabolic syndrome, including hypertension, hyperuricemia, hyperglycemia, and systemic and hepatic TG accumulation. OA alone also induced glomerular hypertension, and SB alone induced insulin resistance. SB + OA induced a combined phenotype including metabolic and renal alterations induced by SB or OA alone and in addition also acted synergistically on systemic and glomerular pressure, plasma glucose, hepatic TG, and oxidative stress. These findings explain why high concentrations of fructose are required to induce greater metabolic changes and renal disease in rats whereas humans, who lack uricase, appear to be much more sensitive to the effects of fructose.
含糖饮料（SB）中的果糖会增加代谢和心脏-肾脏疾病的风险，这些影响部分是由于尿酸（UA）的二次升高所介导的。啮齿动物有活性的尿酸酶，因此需要大剂量的果糖来增加血浆 UA，并诱导代谢综合征和肾脏血流动力学改变。因此，我们假设在尿酸酶抑制的情况下，果糖对大鼠的影响可能会增强。在 8 周的时间里，研究了 4 组雄性 Sprague-Dawley 大鼠（每组 n = 7）：水+载体（V）、水+氧嗪酸钾（OA；750mg/kg BW）、含糖饮料（SB；11%果糖-葡萄糖混合物）+V 和 SB+OA。在实验结束时，评估了系统血压、血浆 UA、甘油三酯（TG）、葡萄糖和胰岛素、肾小球血流动力学、肾脏结构损伤、肾脏皮质和肝脏 UA、TG、氧化应激标志物、线粒体 DNA、果糖激酶和脂肪肝合成酶蛋白表达。慢性高尿酸血症和 SB 诱导了代谢综合征的特征，包括高血压、高尿酸血症、高血糖和全身及肝脏 TG 蓄积。OA 单独也诱导了肾小球高血压，而 SB 单独诱导了胰岛素抵抗。SB+OA 诱导了一种联合表型，包括 SB 或 OA 单独诱导的代谢和肾脏改变，以及全身和肾小球压力、血浆葡萄糖、肝脏 TG 和氧化应激的协同作用。这些发现解释了为什么大鼠需要高浓度的果糖才能诱导更大的代谢变化和肾脏疾病，而缺乏尿酸酶的人类对果糖的影响似乎更为敏感。
