The liver is a source of multiple growth factors and hepatokines such as activin-E, angiopoietin-like 4 (ANGPTL4), angiopoietin-like 6 (ANGPTL6), fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15), all of which have been observed to exert systemic effects and contribute to improvement of insulin resistance and enhancement of insulin sensitivity, although the molecular effects of these factors mostly remain to be identified42. The gene discussed is GDF15; the disease is Insulin resistance.