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.

中文翻译：

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GDF15通过恶心和呕吐诱发厌食。

生长分化因子15（GDF15）是一种通过激活后脑GFRAL-RET受体减少食物摄取的细胞因子，已成为抗肥胖疗法的关注目标。内源性GDF15升高与能量平衡紊乱，癌症进展，化疗引起的厌食症和晨吐有关。我们假设GDF15引起呕吐，并且它的厌食作用与此功能有关。在这里，我们检查了三种不同的哺乳动物实验室物种的进食，呕吐和/或催吐样行为，以帮助阐明GDF15在这些行为中的作用。数据显示，GDF15引起桑Sun（麝香mus）呕吐，并在非催吐物种（包括小鼠和瘦或肥胖大鼠）中引起指示恶心/不适（例如厌食和异食癖）的行为。我们还提供了小鼠中的数据，表明GDF15有助于化疗引起的不适。总之，这些结果表明，GDF15通过引起恶心和/或通过催吐神经回路触发厌食。