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Updated: May 17, 2026
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Assessment of the Metabolic Effects of Isocaloric 2:1 Intermittent Fasting in Mice
Published on: November 27, 2019
Gut-derived serotonin is a multifunctional determinant to fasting adaptation
Grzegorz Sumara1, Olga Sumara, Jason K Kim
1Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
Cell Metabolism
|October 23, 2012
Summary
Gut-derived serotonin (GDS) increases during fasting, promoting fat breakdown (lipolysis) and liver glucose production (gluconeogenesis) to maintain energy. Inhibiting GDS may help manage glucose intolerance and type 2 diabetes.
Area of Science:
- Metabolism
- Endocrinology
- Cell Biology
Background:
- Cellular energy release via lipolysis and liver gluconeogenesis is vital for fasting survival.
- Gut-derived serotonin (GDS) plays a role in metabolic regulation.
Purpose of the Study:
- To investigate the role of gut-derived serotonin (GDS) in regulating energy metabolism during fasting.
- To elucidate the mechanisms by which GDS influences lipolysis and gluconeogenesis.
Main Methods:
- Studied GDS regulation and its effects in mouse models during fasting.
- Utilized molecular and cellular assays to examine GDS signaling pathways in adipocytes and hepatocytes.
- Investigated the role of Htr2b receptor, hormone-sensitive lipase, FBPase, G6Pase, and Glut2.
Main Results:
- Gut-derived serotonin (GDS) is upregulated during fasting in mice.
- GDS signals via Htr2b in adipocytes to enhance lipolysis by activating hormone-sensitive lipase.
- GDS signaling through Htr2b in hepatocytes boosts gluconeogenesis (FBPase, G6Pase) and prevents glucose uptake (Glut2).
Conclusions:
- Gut-derived serotonin (GDS) promotes essential fasting adaptations: lipolysis and liver gluconeogenesis.
- GDS signaling opposes glucose uptake, aiding blood glucose homeostasis during fasting.
- Inhibiting GDS synthesis shows potential for improving glucose intolerance and type 2 diabetes.
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