Tsai Vicky Wang-Wei, Brown David A, Breit Samuel N
St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and University of New South Wales, Sydney, NSW, Australia.
Curr Opin Support Palliat Care. 2018 Dec;12(4):404-409. doi: 10.1097/SPC.0000000000000384.
To review recent finding on MIC-1/GDF15 and re-evaluate it as a potential target for the therapy of anorexia/cachexia syndromes.
MIC-1/GDF15 consistently induces anorexia/cachexia in animal models. Its actions on brainstem feeding centers leads to anorexia, inducing prolonged undernutrition and consequent loss of both lean and fat mass. Epidemiological studies by multiple groups have linked substantially elevated serum levels of this cytokine to anorexia/cachexia syndromes in diverse diseases such as cancer, chronic renal and cardiac failure, and chronic obstructive lung disease. These elevated serum levels are similar to those required to induce this syndrome in animals. Recent identifications of its previously elusive receptor as GFRAL, has enhanced understanding of its biology and suggests that modulating the MIC-1/GDF15-GFRAL pathway may be a therapeutic target for anorexia/cachexia syndrome.
Inhibiting MIC-1/GDF15 or its receptor GFRAL are high-value potential targets for treatment of anorexia/cachexia syndrome in patients whose elevated serum levels may justify its use.
回顾近期关于巨噬细胞抑制因子-1/生长分化因子15（MIC-1/GDF15）的研究发现，并重新评估其作为厌食/恶病质综合征治疗潜在靶点的可能性。
在动物模型中，MIC-1/GDF15持续诱发厌食/恶病质。它对脑干进食中枢的作用导致厌食，引起长期营养不足，进而导致瘦体重和脂肪量均减少。多个研究小组的流行病学研究表明，在癌症、慢性肾衰竭、心力衰竭和慢性阻塞性肺疾病等多种疾病中，这种细胞因子的血清水平大幅升高与厌食/恶病质综合征相关。这些升高的血清水平与在动物中诱发该综合征所需的水平相似。最近发现其先前难以捉摸的受体为GFRAL，这增进了对其生物学特性的理解，并表明调节MIC-1/GDF15-GFRAL途径可能是厌食/恶病质综合征的治疗靶点。
对于血清水平升高可能支持其使用的患者，抑制MIC-1/GDF15或其受体GFRAL是治疗厌食/恶病质综合征的高价值潜在靶点。
