Fructose-Rich Diet Is a Risk Factor for Metabolic Syndrome, Proximal Tubule Injury and Urolithiasis in Rats.

Fructose-Rich Diet Is a Risk Factor for Metabolic Syndrome, Proximal Tubule Injury and Urolithiasis in Rats.
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DOI:
10.3390/ijms23010203
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发表时间:
2021-12-24
影响因子:
5.6
通讯作者:
Manitius J
Manitius J
中科院分区:
生物学2区
文献类型:
--
作者:
Flisiński M;Brymora A;Skoczylas-Makowska N;Stefańska A;Manitius J

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过量摄入果糖(FR)会导致肥胖、代谢综合征(MS)和胰岛素抵抗,这些都是肾结石的已知危险因素。流行病学研究表明果糖摄入与尿石症之间存在关联,但其确切机制尚不清楚。将雄性Wistar大鼠分为三组,分别饲喂饲料中FR含量不同的饲料,为期8周:RD (n = 5) -常规饲料,FR <3%;F10 (n = 6) -常规饮食,在饮用水中添加10% Fr;F60 (n = 5) -60% FR作为固体食物。测定血清FR、肌酐(Cr)、胰岛素(Ins)、甘油三酯(Tg)、同型半胱氨酸(HCS)、尿酸(UA)、钙(Ca)、磷酸(Pi)、镁(Mg)、钠(Na)的浓度。收集24 h尿液,进行以下检测:尿液pH值、蛋白尿(PCR)、n -乙酰基-(D)-氨基葡萄糖酶(NAG)、单核细胞化学引诱蛋白(MCP-1)、尿酸(uUAEx)、磷酸盐(uPiEx)、钙(uCaEx)、镁(uMgEx)和钠(uNaEx)的排泄。计算肌酐清除率(CrCl)。采用苏木精、伊红(HE)和von Kossa染色检测肾切片钙沉积。与RD组相比,F10和F60组大鼠表现出较低的CrCl水平、较高的HCS水平和较高的Ins和TG水平等MS的一些特征。有趣的是,F10(液体)饮食比F60(固体)饮食导致更高的血清Ins水平。与RD相比,F10和F60显示尿中MCP-1和NAG的排泄量较高,提示近端小管炎症损伤。与RD相比,F10和F60显示明显较低的uUAEx,尽管在UA的清除率和部分排泄方面没有差异。F60对RD诱导的重度磷尿(30x)、钠尿(4x)和轻度钙尿。F10对RD诱导的钙尿(3×)、磷尿(2×)和轻度钠尿。F10组和F60组分别有2只大鼠的小管和间质出现磷酸钙结石。发生结石的大鼠的特点是血清胰岛素浓度明显升高,尿中钙和镁的排泄明显增加。富含果糖的饮食可能促进近端小管损伤和代谢综合征引起的钙结石的发生。
Excessive consumption of fructose (FR) leads to obesity, metabolic syndrome (MS) and insulin resistance, which are known risk factors for kidney stones. The epidemiological study has suggested the association between fructose consumption and urolithiasis, but the precise mechanism is still not well understood. Male Wistar rats were assigned for 8 weeks to three groups with different FR content in diet: RD (n = 5)—regular diet with a FR <3%; F10 (n = 6)—regular diet with an addition of 10% Fr in drinking water; F60 (n = 5)—60% FR as a solid food. Serum concentration of FR, creatinine (Cr), insulin (Ins), triglycerides (Tg), homocysteine (HCS), uric acid (UA), calcium (Ca), phosphate (Pi), magnesium (Mg) and sodium (Na) were measured. Based on 24 h urine collection the following tests were performed: urine pH, proteinuria (PCR), excretion of N-Acetyl-(D)-Glucosaminidase (NAG), monocyte chemoattractant protein (MCP-1), uric acid (uUAEx), phosphate (uPiEx), calcium (uCaEx), magnesium (uMgEx) and sodium (uNaEx). The creatinine clearance (CrCl) was calculated. Calcium deposits in kidney sections were examined using hematoxylin and eosin (HE) and von Kossa stains. The rats on F10 and F60, as compared to the RD diet, showed a tendency for lower CrCl, higher HCS level and some features of MS as higher Ins and TG levels. Interestingly, F10 (fluid) versus F60 (solid) diet led to higher serum Ins levels. F10 and F60 versus RD demonstrated higher urinary excretion of MCP-1 and NAG which were suggestive for inflammatory injury of the proximal tubule. F10 and F60 as compared to RD showed significantly lower uUAEx, although there were no differences in clearance and fractional excretion of UA. F60 versus RD induced severe phosphaturia (>30×) and natriuria (4×) and mild calciuria. F10 versus RD induced calciuria (3×), phosphaturia (2×) and mild natriuria. Calcium phosphate stones within the tubules and interstitium were found only in rats on FR diet, respectively, in two rats from the F10 group and another two in the F60 group. The rats which developed stones were characterized by significantly higher serum insulin concentration and urinary excretion of calcium and magnesium. A fructose-rich diet may promote development of calcium stones due to proximal tubule injury and metabolic syndrome.
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