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Python metabolomics uncovers a conserved postprandial metabolite and gut-brain feeding pathway
Biorxiv : the Preprint Server for Biology
|January 16, 2026
Summary
Pythons reveal a novel metabolite, para-tyramine-O-sulfate (pTOS), that significantly increases after meals. This metabolite suppresses appetite and reduces body weight in mice, highlighting a conserved link between nutrient intake and energy balance.
Area of Science:
- Metabolomics
- Neuroendocrinology
- Microbiome research
Background:
- Mammals typically eat small, frequent meals.
- Pythons display extreme feeding and fasting, offering a unique model for postprandial studies.
Purpose of the Study:
- To identify molecular mediators of the postprandial response in pythons.
- To investigate the role of para-tyramine-O-sulfate (pTOS) in appetite regulation.
Main Methods:
- Untargeted metabolomics in pythons.
- Microbiome analysis.
- Administration of pTOS in mice and obese mice models.
- Neural activation studies in the hypothalamus.
Main Results:
- Circulating pTOS levels increased >1,000-fold in pythons post-meal.
- pTOS production is microbiome-dependent, derived from dietary tyrosine.
- pTOS activates ventromedial hypothalamus (VMH) neurons in pythons and mice.
- pTOS administration suppressed food intake and body weight in diet-induced obese mice.
Conclusions:
- pTOS is a conserved postprandial anorexigenic metabolite.
- pTOS links nutrient intake to energy balance through VMH neural pathways.
- This discovery opens new avenues for understanding and treating metabolic disorders.
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