Breit Samuel N, Tsai Vicky W
St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and School of Clinical Medicine, University of New South Wales, Sydney, Australia.
Nat Metab. 2025 Aug 18. doi: 10.1038/s42255-025-01353-3.
Growth differentiation factor 15 (GDF15; also known as macrophage-inhibitory cytokine-1) is a stress-responsive cytokine that is overexpressed under a broad range of conditions. It has a role in regulating appetite and body weight and is an aetiological factor in anorexia-cachexia syndromes, as well as nausea and vomiting during pregnancy. Long after its original cloning, its receptor was identified as GFRAL, a distant member of the GDNF receptor family within the TGFβ superfamily, with RET as its co-receptor. Both of these are highly localized to specific hindbrain regions. Although many of GFRAL's metabolic changes may be linked to its effect on suppressing appetite, recent findings suggest that GDF15 also independently regulates energy expenditure and insulin sensitivity. Here, we review recent literature and provide updates on the current understanding of GDF15 biology and its therapeutic applications in health and metabolic diseases.
生长分化因子15（GDF15；也称为巨噬细胞抑制细胞因子-1）是一种应激反应性细胞因子，在多种条件下都会过度表达。它在调节食欲和体重方面发挥作用，是厌食-恶病质综合征以及孕期恶心和呕吐的病因之一。在其最初克隆很久之后，其受体被鉴定为GFRAL，它是转化生长因子β（TGFβ）超家族中胶质细胞源性神经营养因子（GDNF）受体家族的一个远亲成员，RET作为其共受体。这两者都高度定位于特定的后脑区域。尽管GFRAL的许多代谢变化可能与其抑制食欲的作用有关，但最近的研究结果表明，GDF15也独立调节能量消耗和胰岛素敏感性。在此，我们综述了近期文献，并提供了关于GDF15生物学及其在健康和代谢性疾病中的治疗应用的最新认识。
