挖掘瘦素信号通路在恶病质中的治疗潜力。
Exploiting the therapeutic potential of leptin signaling in cachexia.
作者信息
Mak Robert H, Cheung Wai W, Gertler Arieh
机构信息
aDivision of Pediatric Nephrology, Rady Children's Hospital San Diego, University of California San Diego, La Jolla, California, USA bInstitute of Biochemistry, Food Science and Nutrition, Hebrew University of Jerusalem, Rehovot, Israel.
出版信息
Curr Opin Support Palliat Care. 2014 Dec;8(4):352-7. doi: 10.1097/SPC.0000000000000092.
PURPOSE OF REVIEW
The anorexia-cachexia syndrome is a complication of many chronic conditions including cancer, chronic obstructive pulmonary disease, congestive heart failure, and chronic kidney disease (CKD). Leptin levels are significantly elevated in CKD patients and are associated with markers of poor nutritional status as well as mortality and morbidity. This review will focus on the mechanism and exploit the therapeutic potential of leptin signaling in CKD-associated cachexia.
RECENT FINDINGS
Studies in db/db mice show that the lack of leptin receptor is protective against CKD-induced cachexia. Blockade of leptin's downstream mediators, such as melanocortin-4 receptor, attenuated CKD-associated cachexia. Pegylation of leptin antagonists resulted in a potent and effective long-acting reagents suitable for in-vivo studies or therapies. Pegylated leptin antagonist treatment ameliorates CKD-associated cachexia in mice.
SUMMARY
Leptin antagonism may represent a viable therapeutic strategy for cachexia in CKD.
综述目的
恶病质综合征是包括癌症、慢性阻塞性肺疾病、充血性心力衰竭和慢性肾脏病（CKD）在内的多种慢性疾病的并发症。CKD患者的瘦素水平显著升高，且与营养状况不佳的指标以及死亡率和发病率相关。本综述将聚焦于CKD相关性恶病质中瘦素信号传导的机制及探索其治疗潜力。
最新发现
对db/db小鼠的研究表明，缺乏瘦素受体可预防CKD诱导的恶病质。阻断瘦素的下游介质，如黑皮质素-4受体，可减轻CKD相关性恶病质。瘦素拮抗剂的聚乙二醇化产生了一种适用于体内研究或治疗的强效长效试剂。聚乙二醇化瘦素拮抗剂治疗可改善小鼠的CKD相关性恶病质。
总结
瘦素拮抗作用可能是CKD恶病质的一种可行治疗策略。
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