Internal Medicine Research Unit, Pfizer Worldwide Research, Development & Medical, Cambridge, MA 02139, USA.
Comparative Medicine, Pfizer Worldwide Research, Development & Medical, Cambridge, MA 02139, USA.
Cells. 2022 Mar 23;11(7):1073. doi: 10.3390/cells11071073.
Growth and differentiation factor 15 (GDF15) is a cytokine reported to cause anorexia and weight loss in animal models. Neutralization of GDF15 was efficacious in mitigating cachexia and improving survival in cachectic tumor models. Interestingly, elevated circulating GDF15 was reported in patients with pulmonary arterial hypertension and heart failure, but it is unclear whether GDF15 contributes to cachexia in these disease conditions. In this study, rats treated with monocrotaline (MCT) manifested a progressive decrease in body weight, food intake, and lean and fat mass concomitant with elevated circulating GDF15, as well as development of right-ventricular dysfunction. Cotreatment of GDF15 antibody mAb2 with MCT prevented MCT-induced anorexia and weight loss, as well as preserved lean and fat mass. These results indicate that elevated GDF15 by MCT is causal to anorexia and weight loss. GDF15 mAb2 is efficacious in mitigating MCT-induced cachexia in vivo. Furthermore, the results suggest GDF15 inhibition is a potential therapeutic approach to alleviate cardiac cachexia in patients.
生长分化因子 15（GDF15）是一种细胞因子，据报道它会导致动物模型出现厌食和体重减轻。中和 GDF15 在减轻恶病质和提高恶病质肿瘤模型的生存率方面是有效的。有趣的是，在肺动脉高压和心力衰竭患者中报告了循环 GDF15 水平升高，但尚不清楚 GDF15 是否会导致这些疾病状态下的恶病质。在这项研究中，给予单环酸酯（MCT）的大鼠表现出体重、食物摄入以及瘦体重和脂肪量逐渐减少，同时循环 GDF15 升高，以及右心室功能障碍的发展。用 GDF15 抗体 mAb2 与 MCT 共同治疗可预防 MCT 诱导的厌食和体重减轻，并保持瘦体重和脂肪量。这些结果表明，MCT 引起的 GDF15 升高是导致厌食和体重减轻的原因。GDF15 mAb2 在体内有效减轻 MCT 诱导的恶病质。此外，这些结果表明 GDF15 抑制可能是一种缓解患者心脏恶病质的潜在治疗方法。
