GDF15 Induces Anorexia through Nausea and Emesis.

Area of Science:

• Neuroscience
• Endocrinology
• Pharmacology

Background:

• Growth differentiation factor 15 (GDF15) is a cytokine implicated in appetite regulation and associated with various health conditions.
• GDF15 activates hindbrain GFRAL-RET receptors, making it a target for anti-obesity therapies.
• Elevated GDF15 levels correlate with energy balance issues, cancer, and chemotherapy-induced anorexia.

Purpose of the Study:

• To investigate the hypothesis that GDF15 induces emesis (vomiting) and that its anorectic (appetite-reducing) effects are linked to this function.
• To elucidate the role of GDF15 in feeding and emetic behaviors across different mammalian species.

Main Methods:

• Experiments were conducted on three mammalian species: Suncus murinus (musk shrews), mice, and rats (lean and obese).
• Feeding behavior, emesis, and emetic-like behaviors (e.g., anorexia, pica) were monitored.
• Data were analyzed to determine GDF15's impact on these physiological responses.

Main Results:

• GDF15 administration induced emesis in musk shrews.
• In non-emetic species (mice, rats), GDF15 triggered behaviors indicative of nausea/malaise, such as anorexia and pica.
• GDF15 was shown to contribute to chemotherapy-induced malaise in mice.

Conclusions:

• GDF15's anorectic effects are mediated by the induction of nausea and/or engagement of emetic neurocircuitry.
• These findings highlight GDF15's dual role in triggering anorexia through nausea and potentially engaging vomiting pathways.
• The study provides insights into GDF15's physiological functions relevant to appetite control and therapeutic development.