高果糖引起的脂肪肝大鼠肾脏脂质合成相关基因和蛋白的表达

Renal Lipid Accumulation and Expression of the Proteins/Genes Responsible for Fatty Acid Synthesis in Rats with Fatty Liver Induced by Fructose Overconsumption

大量研究表明,高果糖可引起脂肪肝,但对肾脏脂质代谢的影响尚不清楚。该实验研究给予10%果糖水5周后诱导的脂肪肝大鼠肾脏的脂质代谢情况,并探讨其可能机制。将16只雄性SD大鼠随机分为正常组(con)和果糖组(fru),果糖组给予10%(W/V)果糖水,第5周末称体重、取血、处死,检测血浆GLU、TG、TC和INSULIN含量。取肾脏、肝脏和白色脂肪称重,采用形态学方法观察肝脏和肾脏脂质沉积情况,酶法测其TG、TC含量,以Real time-PCR检测肾脏、肝脏中脂质合成和脂质氧化相关基因水平,以Western blot检测肾、肝细胞核脂质合成转录因子的蛋白表达。结果显示,果糖组大鼠血浆TG、INSULIN明显升高,并出现肥胖体征,肝脏脂质沉积严重,其调控脂质合成的两个关键的转录因子ChREBP和SREBP1c mRNA和核蛋白表达都明显升高,并且它们靶向的脂质合成相关酶FAS、ACC1、SCD1 mRNA表达也显著增加。但是,在肾脏中,高果糖没有引起TG含量的变化,调控脂质重新合成的基因和蛋白的表达也未发生变化。因此,与果糖致脂肪肝不同,高果糖饮食并没有造成肾脏的脂质沉积和脂质合成相关基因、蛋白的变化。

Chronically high consumption of fructose in rodents leads to fatty liver. However, it is still unknown whether fructose overconsumption affects renal lipid metabolism. Here, we found that treatment of rats with 10% fructose in drinking water over 5 weeks induced excess hepatic triglyceride deposition, further investigated the effects and mechanisms of fructose overconsumption on renal lipid metabolism by comparing to those in the liver in rats. Sixteen male SD rats were divided into two groups： （1） water control with free access to water; （2） fructose with free access to 10% fructose in drinking water （W/V, prepared daily）. The duration of the experiment was 5 weeks. On day 35, animals were weighed, then blood samples were collected by retroorbital venous puncture under ether anesthesia for determination of plasma concentrations of glucose, insulin, total cholesterol and triglyceride. Immediately thereafter, animals were killed. Livers, kidneys, epididymal and perirenal white adipose tissues were collected and weighed. The indexes of lipid in liver and kidney were determined histologically and enzymatically. Gene expressions involved in lipid synthesis and oxidation were analyzed by Real time-PCR. Protein expressions of transcriptional regulators involved in lipid metabolism were analyzed by Western blot. The results showed that treatment of rats with 10% fructose in drinking water over 5 weeks induced excess hepatic triglyceride deposition, accompanied by increases in plasma concentrations of triglyceride and insulin, as well as adiposity. Further, hepatic mRNA and/or nuclear protein expressions of two key transcriptional regulators carbohydrate response element binding protein （ChREBP） and sterol regulatory element-binding protein （SREBP） 1 e, and their targeted genes responsible for de novo fatty acid synthesis, were activated. Surprisingly, the lipid content and expression of these proteins/genes in the kidneys were not altered by fructose feeding. Therefore, unlike the liver, fructose overconsumption does not alter renal lipid accumulation and expression of the proteins/genes responsible for de novo fatty acid synthesis in rats.