GDF15 Induces Anorexia through Nausea and Emesis.

Growth differentiation factor 15 (GDF15) is a cytokine that reduces food intake through activation of hindbrain GFRAL-RET receptors and has become a keen target of interest for anti-obesity therapies. Elevated endogenous GDF15 is associated with energy balance disturbances, cancer progression, chemotherapy-induced anorexia, and morning sickness. We hypothesized that GDF15 causes emesis and that its anorectic effects are related to this function. Here, we examined feeding and emesis and/or emetic-like behaviors in three different mammalian laboratory species to help elucidate the role of GDF15 in these behaviors. Data show that GDF15 causes emesis in Suncus murinus (musk shrews) and induces behaviors indicative of nausea/malaise (e.g., anorexia and pica) in non-emetic species, including mice and lean or obese rats. We also present data in mice suggesting that GDF15 contributes to chemotherapy-induced malaise. Together, these results indicate that GDF15 triggers anorexia through the induction of nausea and/or by engaging emetic neurocircuitry.
Competing Interests: Declaration of Interests B.C.D. receives research funding from Eli Lilly & Co. and Pfizer, Inc. and provided remunerated consultancy services for cachexia-related projects for Pfizer, Inc., not supporting these studies. R.P.D. is a scientific advisory board member and received funds from Xeragenx LLC (St. Louis, NY) and Balchem, New Hampton, New York that were not used in support of these studies. M.R.H. receives research funding from Zealand Pharma, Novo Nordisk, Eli Lilly & Co., and Boehringer Ingelheim that was not used in support of these studies. H.J.G. is a consultant and advisory board member for Novo Nordisk and receives research support from Pfizer, Inc. that was not used to support these studies. T.B., M.R.H., B.C.D., and R.P.D. are co-inventors and owners of a patent for a proprietary compound related to the GDF15-GFRAL system (serial #: 62/801,391). No other competing interests are declared.
(Copyright © 2019. Published by Elsevier Inc.)