GDF15

GDF15 Full Name

growth differentiation factor 15

GDF15 Introduction

Definition and ClassificationGrowth Differentiation Factor 15 (GDF15) is a divergent member of the transforming growth factor-beta (TGF-$\beta$) superfamily of cytokines. Historically, it has been referred to by various names, including Macrophage Inhibitory Cytokine-1 (MIC-1), NSAID-activated gene-1 (NAG-1), and Placental Bone Morphogenetic Protein (PLAB), reflecting the diverse contexts in which it was independently discovered. Unlike other members of the TGF-$\beta$ family that play direct roles in tissue development, GDF15 is primarily recognized today as a stress-responsive cytokine. It circulates in the blood as a homodimer and acts as a critical signal of cellular distress and metabolic state.

Figure 1. Strcuture of growth differentiation factor 15.

Pathological Significance and Disease Biomarker
The strong induction of GDF15 during pathological states makes it a highly sensitive, though non-specific, clinical biomarker. Its levels are dramatically elevated in numerous conditions, including cancer, cardiovascular diseases, chronic kidney disease, and non-alcoholic fatty liver disease (NAFLD). In oncology, it is particularly associated with cancer cachexia, a severe wasting syndrome, where its anorectic effect drives weight and muscle loss. Elevated GDF15 also correlates with the risk of cardiovascular events and mortality, providing prognostic value independent of traditional markers.

Clinical Applications and Therapeutic Targeting
The GDF15-GFRAL pathway represents a compelling therapeutic target for metabolic disorders. Antagonizing this pathway (e.g., with GFRAL-neutralizing antibodies) is being investigated to treat cancer cachexia and counteract the weight-loss side effects of drugs like GLP-1 receptor agonists. Conversely, because GDF15 itself reduces appetite and body weight, engineered long-acting analogs are in development as potential novel anti-obesity agents. The measurement of circulating GDF15 is already used in research contexts and holds promise for future clinical use in risk stratification and monitoring disease progression.

Alternate Names for GDF15

GDF15; growth differentiation factor 15; PDF; MIC1; PLAB; MIC-1; NAG-1; PTGFB; GDF-15; growth/differentiation factor 15