Jiang Yao, Zhang Jingjing, Yuan Yanggang, Zha Xiaoming, Xing Changying, Shen Chong, Shen Zhixiang, Qin Chao, Zeng Ming, Yang Guang, Mao Huijuan, Zhang Bo, Yu Xiangbao, Sun Bin, Ouyang Chun, Xu Xueqiang, Ge Yifei, Wang Jing, Zhang Lina, Cheng Chen, Yin Caixia, Zhang Jing, Chen Huimin, Ma Haoyang, Wang Ningning
Department of Nephrology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, 210029, China.
Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, 210029, China.
Sci Rep. 2016 Jun 16;6:27918. doi: 10.1038/srep27918.
Leptin is an adipokine that regulates various metabolism, but its association with secondary hyperparathyroidism (SHPT), a clinical manifestation of chronic kidney disease-mineral and bone disorder (CKD-MBD), remains obscure. Parathyroidectomy (PTX) is recommended for severe SHPT patients. Here, the associations between circulating leptin and clinical characteristics in CKD patients were investigated. Effects of PTX on leptin production were analyzed in vivo and in vitro. Controls and CKD patients had approximate serum leptin levels in that a larger proportion of CKD patients with body mass index (BMI) <23 kg/m(2). Serum leptin was related to anemia, albumin, and bone metabolism disorders in CKD patients. Lower intact parathyroid hormone (PTH) was related with higher leptin in PTX patients group. Severe SHPT inhibited uremia-enhanced leptin production in 3T3-L1 adipocytes, which was attenuated after PTX. High levels of PTH were found to reduce Akt phosphorylation and leptin production in vitro but high levels of calcium and phosphorus were not. Successful PTX was found to improve anemia and malnutrition in severe SHPT patients, and this was correlated with increased circulating leptin levels via up-regulated Akt signaling in adipocytes. These findings indicated the therapeutic potential of leptin and related target pathway for improving survival and quality of life in CKD.
瘦素是一种调节多种代谢的脂肪因子，但其与慢性肾脏病-矿物质和骨异常（CKD-MBD）的临床表现——继发性甲状旁腺功能亢进（SHPT）之间的关联仍不清楚。对于重度SHPT患者，建议进行甲状旁腺切除术（PTX）。在此，研究了CKD患者循环瘦素与临床特征之间的关联。在体内和体外分析了PTX对瘦素产生的影响。对照组和CKD患者的血清瘦素水平相近，因为更大比例的CKD患者体重指数（BMI）<23kg/m²。血清瘦素与CKD患者的贫血、白蛋白及骨代谢紊乱有关。在PTX患者组中，较低的完整甲状旁腺激素（PTH）与较高的瘦素相关。重度SHPT抑制了3T3-L1脂肪细胞中尿毒症增强的瘦素产生，PTX后这种抑制作用减弱。体外研究发现高水平的PTH会降低Akt磷酸化和瘦素产生，但高水平的钙和磷则不会。研究发现成功的PTX可改善重度SHPT患者的贫血和营养不良，这与通过上调脂肪细胞中的Akt信号增加循环瘦素水平相关。这些发现表明瘦素及相关靶途径在改善CKD患者生存率和生活质量方面具有治疗潜力。
