Beneficial effects of isoflavones in the kidney of obese rats are mediated by PPAR-gamma expression

Several studies have demonstrated an association between the altered lipid metabolism and development of kidney injury because of a high-fat diet. Since the addition of fructose instead of glucose is common in the Occident diet, in this experimental model of obesity in rats, we opted for the high-lipidic-fructose diet (DH). After two months of ingestion, there was an expansion of the visceral fat, which was associated with long-term metabolic disorders, such as sustained hyperglycemia, insulin resistance, polyuria, dyslipidemia (hypercholesterolemia and hypertriglyceridemia), and hypertension. Additionally, we found a decrease in the renal blood flow (RBF), an increase in the renal vascular resistance (RVR). Biochemical markers of CKD were detected, there was inflammatory cell infiltration with elevated expression of proinflammatory cytokines (TNF-α, IL-6, and IL-1β), activation of renin-angiotensin system, and oxidative/nitrosative stress. Notably, the rats exposed to the DH diet for 120 days and treated concomitantly after 60 days with isoflavones (DH+ISO) were able to revert the metabolic parameters, renal alterations, and oxidative/nitrosative stress. The beneficial effects of the isoflavones in the kidney of the obese rats were found to be dependent on the expression of PPAR-gamma. The raw data from the experiments were attached.多项研究已证实，脂质代谢异常与高脂饮食诱导的肾损伤发生存在关联。鉴于西方膳食中普遍以果糖替代葡萄糖作为甜味来源，本研究在大鼠肥胖实验模型中采用了高脂果糖饮食（high-lipidic-fructose diet, DH）。大鼠持续摄入该饮食2个月后，出现内脏脂肪堆积，并伴随一系列长期代谢紊乱，包括持续性高血糖、胰岛素抵抗、多尿、血脂异常（高胆固醇血症与高甘油三酯血症）及高血压。此外，本研究还观察到肾血流量（renal blood flow, RBF）下降、肾血管阻力（renal vascular resistance, RVR）升高；检测到慢性肾脏病（chronic kidney disease, CKD）相关生化标志物异常，同时存在炎性细胞浸润、促炎细胞因子（肿瘤坏死因子-α、白细胞介素-6及白细胞介素-1β）表达上调、肾素-血管紧张素系统激活，以及氧化/亚硝化应激反应。值得注意的是，喂食DH饮食120天且在造模60天后同步给予异黄酮干预的大鼠（DH+ISO组），其代谢指标、肾脏损伤及氧化/亚硝化应激状态均得到逆转。进一步研究发现，异黄酮对肥胖大鼠肾脏的保护作用依赖于过氧化物酶体增殖物激活受体γ（PPAR-γ）的表达。本实验的原始数据已随文附上。