Growth/differentiation factor 15 is a protein that is encoded by the GDF15 gene.
It is a protein belonging to the transforming growth factor beta superfamily.
Under normal conditions, GDF15 is expressed in low concentrations in most organs.
GDF-15 is minimally expressed in most somatic tissues under normal physiological conditions but is highly expressed in the placenta.
GDF-15 is upregulated because of injury of organs such as liver, kidney, heart and lung.
GDF15 has a role in regulating inflammatory pathways and to be involved in regulating apoptosis, angiogenesis, cell repair and cell growth, which are biological processes observed in cardiovascular and neoplastic disorders.
GDF-15 modulate inflammation and systemic inflammatory response and has a pivotal mechanism for the development of cancer cachexia.
GDF15 has shown to be a strong prognostic protein in patients with different diseases such as heart diseases and cancer.
In cardiovascular tissues it is shown that GDF15 concentrations increase in response to atherosclerosis, ischemia/reperfusion injury and heart failure.
In patients with coronary artery disease (CAD), GDF15 is shown to be associated with adverse outcome such as mortality, myocardial infarction, stroke and with bleeding.
Growth Differentiation Factor 15 (GDF-15), also known as macrophage inhibitory cytokine-1 (MIC-1).
It is a divergent member of the transforming growth factor-β (TGF-β) superfamily.
GDF-15 levels increase significantly in response to cellular stress and various pathological conditions, including inflammation, myocardial ischemia, and cancer.
GDF-15 acts through its receptor, glial cell-derived neurotrophic factor (GDNF) family receptor α-like (GFRAL), which is primarily expressed in the brainstem.
This interaction is known to regulate energy homeostasis by inducing anorexia and weight loss, making GDF-15.
GDF-15 has immunomodulatory properties and is involved in maintaining immune tolerance.
Elevated levels of GDF-15 are associated with poor prognosis in various diseases, including cardiovascular diseases and cancer, making it a valuable biomarker for disease severity and prognosis.
GDF-15 is a multifunctional cytokine with significant roles in metabolism, immune regulation, and disease pathology, and it is being explored as a therapeutic target in several conditions.
Elevated GDF15 levels in diseases such as cancer and heart disease may be the result of inflammation caused by these diseases.
GDF15 is necessary for surviving both bacterial and viral infections, as well as sepsis.
Its protective effects are largely independent of pathogen control or the magnitude of inflammatory response, suggesting a role in disease tolerance.
Metformin causes increased levels of GDF15.
This increase mediates the effect of body weight loss by metformin: weight loss is promoted by maintaining energy expenditure in addition to appetite suppression.
Elevations in GDF15 reduce food intake and body mass in animal models through binding to glial cell-derived neurotrophic factor family receptor alpha-like (GFRAL) and the recruitment of the receptor tyrosine kinase RET in the hindbrain.
Metformin and exercise increase circulating levels of GDF15.
GDF15 might also exert anti-inflammatory effects.
GDF15 a candidate to treat many metabolic diseases, including obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease, cardiovascular disease and cancer cachexia.
Treatment of rodents fed a high-fat diet with recombinant growth differentiating factor 15 (GDF15) reduces obesity and improves glycemic control through glial-cell-derived neurotrophic factor family receptor α-like (GFRAL)-dependent suppression of food intake.
GDF15 is associated as a causal factor in hyperemesis gravidarum, a severe form of morning sickness.
GDF15 is being evaluated as a therapeutic target for treatment of cancer cachexia.
The anti-GDF15 monoclonal antibody ponsegromab led to significant increases in body weight in patients with non-small cell lung cancer, pancreatic cancer, and colorectal cancer.