Famsin, a novel gut-secreted hormone, contributes to metabolic adaptations to fasting via binding to its receptor OLFR796
Famsin, a novel gut-secreted hormone, contributes to metabolic adaptations to fasting via binding to its receptor OLFR796
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DOI：
10.1038/s41422-023-00782-7
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发表时间：
2023-02
期刊：
影响因子：
44.1
通讯作者：
Aijun Long;Yang Liu;X. Fang;Liangjie Jia;Zhiyuan Li;Jiang Hu;Shuang Wu;Chao Chen;Ping Huang;Yiguo Wang
中科院分区：
文献类型：
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作者：
Aijun Long;Yang Liu;X. Fang;Liangjie Jia;Zhiyuan Li;Jiang Hu;Shuang Wu;Chao Chen;Ping Huang;Yiguo Wang
肠道负责营养吸收，并在进食期间协调不同器官的代谢，这一过程部分由甜菜碱衍生的激素控制。然而，目前还不清楚肠道是否在禁食期间的代谢中起重要作用。在这里，我们已经确定了一种新的激素，famsin，它是从肠道分泌的，并促进代谢适应禁食。从机制上讲，famsin在禁食期间从单次跨膜蛋白Gm 11437脱落，然后结合嗅觉受体OLFR 796，以激活细胞内钙动员。该famsin-OLFR 796信号传导轴促进能量动员的胚胎发生和生酮，以及禁食期间能量保存的迟钝。此外，通过抗体中和法辛改善了糖尿病模型中的血糖谱，这将法辛鉴定为用于治疗糖尿病的潜在治疗靶标。因此，我们的研究结果表明，肠道和其他器官之间通过famsin-OLFR 796信号轴的通信对于禁食的代谢适应至关重要。
The intestine is responsible for nutrient absorption and orchestrates metabolism in different organs during feeding, a process which is partly controlled by intestine-derived hormones. However, it is unclear whether the intestine plays an important role in metabolism during fasting. Here we have identified a novel hormone, famsin, which is secreted from the intestine and promotes metabolic adaptations to fasting. Mechanistically, famsin is shed from a single-pass transmembrane protein, Gm11437, during fasting and then binds OLFR796, an olfactory receptor, to activate intracellular calcium mobilization. This famsin-OLFR796 signaling axis promotes gluconeogenesis and ketogenesis for energy mobilization, and torpor for energy conservation during fasting. In addition, neutralization of famsin by an antibody improves blood glucose profiles in diabetic models, which identifies famsin as a potential therapeutic target for treating diabetes. Therefore, our results demonstrate that communication between the intestine and other organs by a famsin-OLFR796 signaling axis is critical for metabolic adaptations to fasting.