2. Academic Validation
  3. 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

  • Cell Res. 2023 Apr;33(4):273-287. doi: 10.1038/s41422-023-00782-7.
Aijun Long # 1,  Yang Liu # 1,  Xinlei Fang 1,  Liangjie Jia 1,  Zhiyuan Li 1,  Jiang Hu 2,  Shuang Wu 2,  Chao Chen 3,  Ping Huang 4,  Yiguo Wang 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Membrane Biology, MOE Key Laboratory of Bioinformatics, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • 2 The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
  • 3 The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
  • 4 The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China. [email protected].
  • 5 State Key Laboratory of Membrane Biology, MOE Key Laboratory of Bioinformatics, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China. [email protected].
  • # Contributed equally.
PMID: 36806353 DOI: 10.1038/s41422-023-00782-7
Abstract

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.

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