Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
Biochem Biophys Res Commun. 2012 Mar 9;419(2):244-9. doi: 10.1016/j.bbrc.2012.02.001. Epub 2012 Feb 8.
Fructose induces several kinds of human metabolic disorders; however, information regarding fructose-induced kidney injury is still limited. This study examined fructose-induced kidney injury in mice and clarified the differential susceptibility of three mouse strains: C57Bl/6J, CBA/JN and DBA/2N. In this study all mice were fed with an equal calorie count for sixteen weeks to remove the influence of total energy intake from metabolic effects by fructose-feeding. Only DBA/2N mice, but not C57Bl/6J and CBA/JN mice, fed with fructose displayed tubulointerstitial fibrosis localized on the outer cortex of the kidney together with the increase of mRNA expression of Kim1 and Ngal in the absence of distinct glomerular lesions and albuminuria - decidedly different from diabetic nephropathy. In time-course study of DBA/2N mice fed with fructose diet, the inflammation and fibrosis in the outer cortex of the kidney were enhancing after eight weeks, in parallel with the accumulation of oxidative stress. This progression of renal damage in DBA/2N mice was accompanied with increasing mRNA expression of GLUT5. These results suggest that the responsiveness of GLUT5 expression to fructose at the kidney is one of pivotal roles for the progression of fructose-induced kidney injury.
果糖可引起多种人类代谢紊乱；然而，关于果糖引起的肾脏损伤的信息仍然有限。本研究在小鼠中研究了果糖引起的肾脏损伤，并阐明了三种小鼠品系（C57Bl/6J、CBA/JN 和 DBA/2N）的不同易感性。在本研究中，所有小鼠均接受相同热量的饮食喂养 16 周，以消除果糖喂养对代谢效应的总能量摄入的影响。只有 DBA/2N 小鼠，而不是 C57Bl/6J 和 CBA/JN 小鼠，在没有明显肾小球病变和白蛋白尿的情况下，显示出肾小管间质纤维化，局限于肾脏的外皮质，同时 Kim1 和 Ngal 的 mRNA 表达增加-与糖尿病肾病决然不同。在 DBA/2N 小鼠喂食果糖饮食的时间过程研究中，在 8 周后，肾脏外皮质的炎症和纤维化增强，同时氧化应激积累。DBA/2N 小鼠肾脏损伤的这种进展伴随着 GLUT5 mRNA 表达的增加。这些结果表明，肾脏对果糖的 GLUT5 表达的反应性是果糖引起的肾脏损伤进展的关键作用之一。
