Grupo Fisiopatología Endocrina, Área de Endocrinología, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, Travesía da Choupana s/n, 15706, Santiago de Compostela, Spain.
Translational Endocrinology Group, Endocrinology Section, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago (IDIS/CHUS), Santiago de Compostela, Spain.
J Endocrinol Invest. 2024 May;47(5):1139-1154. doi: 10.1007/s40618-023-02232-y. Epub 2023 Nov 13.
Growth differentiation factor 15 (GDF15) is a stress response cytokine that has been proposed as a relevant metabolic hormone. Descriptive studies have shown that plasma GDF15 levels are regulated by short term changes in nutritional status, such as fasting, or in obesity. However, few data exist regarding how GDF15 levels are regulated in peripheral tissues. The aim of the present work was to study the variations on gastric levels of GDF15 and its precursor under different physiological conditions, such as short-term changes in nutritional status or overfeeding achieved by HFD. Moreover, we also address the sex- and age-dependent alterations in GDF15 physiology.
The levels of gastric and plasma GDF15 and its precursor were measured in lean and obese mice, rats and humans by western blot, RT-PCR, ELISA, immunohistochemistry and by an in vitro organ culture system.
Our results show a robust regulation of gastric GDF15 production by fasting in rodents. In obesity an increase in GDF15 secretion from the stomach is reflected with an increase in circulating levels of GDF15 in rats and humans. Moreover, gastric GDF15 levels increase with age in both rats and humans. Finally, gastric GDF15 levels display sexual dimorphism, which could explain the difference in circulating GFD15 levels between males and females, observed in both humans and rodents.
Our results provide clear evidence that gastric GDF15 is a critical contributor of circulating GDF15 levels and can explain some of the metabolic effects induced by GDF15.
生长分化因子 15（GDF15）是一种应激反应细胞因子，被认为是一种相关的代谢激素。描述性研究表明，血浆 GDF15 水平受短期营养状态变化的调节，如禁食或肥胖。然而，关于外周组织中 GDF15 水平如何调节的数据很少。本研究旨在研究不同生理条件下胃 GDF15 及其前体水平的变化，如短期营养状态变化或 HFD 引起的过食。此外，我们还探讨了 GDF15 生理学在性别和年龄上的变化。
通过 Western blot、RT-PCR、ELISA、免疫组织化学和体外器官培养系统，测量瘦鼠和肥胖鼠、大鼠和人类胃和血浆 GDF15 及其前体的水平。
我们的结果显示，禁食可显著调节啮齿动物胃 GDF15 的产生。在肥胖中，胃 GDF15 分泌的增加反映了大鼠和人类循环 GDF15 水平的升高。此外，胃 GDF15 水平在大鼠和人类中随年龄增长而增加。最后，胃 GDF15 水平存在性别二态性，这可以解释在人类和啮齿动物中观察到的循环 GFD15 水平在男性和女性之间的差异。
我们的结果提供了明确的证据，表明胃 GDF15 是循环 GDF15 水平的关键贡献者，并且可以解释 GDF15 诱导的一些代谢效应。
