Fan Chen-Yu, Wang Ming-Xing, Ge Chen-Xu, Wang Xing, Li Jian-Mei, Kong Ling-Dong
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, P. R. China.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, P. R. China.
J Nutr Biochem. 2014 Mar;25(3):353-62. doi: 10.1016/j.jnutbio.2013.11.010. Epub 2013 Dec 4.
High fructose intake causes metabolic syndrome, being an increased risk of chronic kidney disease development in humans and animals. In this study, we examined the influence of betaine on high-fructose-induced renal damage involving renal inflammation, insulin resistance and lipid accumulation in rats and explored its possible mechanisms. Betaine was found to improve high-fructose-induced metabolic syndrome including hyperuricemia, dyslipidemia and insulin resistance in rats with systemic inflammation. Betaine also showed a protection against renal dysfunction and tubular injury with its restoration of the increased glucose transporter 9 and renal-specific transporter in renal brush bolder membrane and the decreased organic anion transporter 1 and adenosine-triphosphate-binding cassette transporter 2 in the renal cortex in this model. These protective effects were relevant to the anti-inflammatory action by inhibiting the production of inflammatory cytokines including interleukin (IL)-1β, IL-18, IL-6 and tumor necrosis factor-α in renal tissue of high-fructose-fed rat, being more likely to suppress renal NOD-like receptor superfamily, pyrin domain containing 3 inflammasome activation than nuclear factor κB activation. Subsequently, betaine with anti-inflammation ameliorated insulin signaling impairment by reducing the up-regulation of suppressor of cytokine signaling 3 and lipid accumulation partly by regulating peroxisome proliferator-activated receptor α/palmityltransferase 1/carnitine/organic cation transporter 2 pathway in kidney of high-fructose-fed rats. These results indicate that the inflammatory inhibition plays a pivotal role in betaine's improvement of high-fructose-induced renal injury with insulin resistance and lipid accumulation in rats.
高果糖摄入会导致代谢综合征，增加人类和动物患慢性肾脏病的风险。在本研究中，我们检测了甜菜碱对高果糖诱导的大鼠肾脏损伤的影响，该损伤涉及肾脏炎症、胰岛素抵抗和脂质蓄积，并探讨了其可能的机制。结果发现，甜菜碱可改善高果糖诱导的代谢综合征，包括全身炎症大鼠的高尿酸血症、血脂异常和胰岛素抵抗。在该模型中，甜菜碱还对肾功能障碍和肾小管损伤具有保护作用，可恢复肾刷状缘膜中葡萄糖转运蛋白9和肾特异性转运蛋白的增加，以及肾皮质中有机阴离子转运蛋白1和三磷酸腺苷结合盒转运蛋白2的减少。这些保护作用与抗炎作用相关，即通过抑制高果糖喂养大鼠肾组织中包括白细胞介素（IL）-1β、IL-18、IL-6和肿瘤坏死因子-α在内的炎性细胞因子的产生，更有可能抑制肾NOD样受体超家族含pyrin结构域的3炎性小体激活而非核因子κB激活。随后，具有抗炎作用的甜菜碱通过减少细胞因子信号转导抑制因子3的上调改善胰岛素信号传导受损，并部分通过调节高果糖喂养大鼠肾脏中的过氧化物酶体增殖物激活受体α/棕榈酰转移酶1/肉碱/有机阳离子转运蛋白2途径减轻脂质蓄积。这些结果表明，炎症抑制在甜菜碱改善高果糖诱导的大鼠胰岛素抵抗和脂质蓄积性肾损伤中起关键作用。
