ArticleClinical and translational medicine2024
The gut microbiota-derived metabolite indole-3-propionic acid enhances leptin sensitivity by targeting STAT3 against diet-induced obesity.
Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Paneth Cells: Recent Updates on Elucidating Therapeutic Implications in Gastroenterological Disease Management.Current medicinal chemistry · 2025Pooled it
- Gut microbial diversity at baseline conditions the clinical, microbiome, and metabolic response to paraprobioticGut microbes · 2026Trial
- Gut microbiota and immunometabolism in obesity.Gut microbes · 2026Review
- Engineered probiotic-derived indole-3-propionic acid inhibits ubiquitination via AHR signaling to treat postmenopausal osteoporosis.Gut microbes · 2026Article
- Gut microbiota metabolic reprogramming drives the development of metabolic diseases in the host.Gut microbes · 2026Review
- Microbiota-Derived Metabolites in Developmental Programming: Bridging Early-Life Gut Microbiota to Childhood Metabolic Disorders.Current medical science · 2026Review
- Pre-treatment with baicalein alleviates the diquat-induced microglial pyroptosis through gut microbiota-derived indole-3-propionic acid and DDX3X/G3BP1 pathway.Cell biology and toxicology · 2026Article
- Proline/serine-rich coiled-coil 1 alleviates atherosclerosis via remodeling tryptophan metabolism mediated by Akkermansia muciniphila.Experimental & molecular medicine · 2026Article
- ExploringBiomolecules & therapeutics · 2026Article
- Melatonin Biosynthesis, Receptors, and the Microbiota-Tryptophan-Melatonin Axis: A Shared Dysbiosis Signature Across Cardiac Arrhythmias, Epilepsy, Malignant Proliferation, and Cognitive Trajectories.International journal of molecular sciences · 2026Article
- Gut microbiota-mediated regulation of lipid metabolism by single herbal medicines: a review focused on cold/hot properties.Chinese medicine · 2026Review
- Gut microbiota-derived tryptophan metabolites: molecular mechanisms, nutritional strategies and implications for swine health.Frontiers in veterinary science · 2026Review
- Microbiome-Driven Mechanisms in Breast Cancer: Emerging Evidence From Gut Microbial Signatures to Therapeutic Response.BioMed research international · 2026Review
- New Horizons in Metabolic Health: Unveiling the Future of Drug Discovery and Development.Endocrine, metabolic & immune disorders drug targets · 2026Review
- Significance of neuroendocrine systems and the gut-brain axis (GBA) in the regulation of obesity.PeerJ · 2026Review
- Clostridium leptum attenuates allergic airway inflammation via tDC‒Treg axis activation in a murine model of gut dysbiosis-associated asthma.Scientific reports · 2025Article
- Intestinal-related substances in obesity regulation: A comprehensive review.World journal of gastrointestinal pharmacology and therapeutics · 2025Review
- Leveraging microbiota-metabolites to reduce inflammation and promote functional recovery following spinal cord injury in female mice.Brain, behavior, & immunity - health · 2025Article
- Oral Multi-Enzymatic Manganese-Carbon Dots Alleviate Sepsis-Associated Lung Injury via the Gut-Lung Axis.ACS nano · 2025Article
- Unraveling the Obesogenic Mechanism of Bisphenol A Through Network Toxicology and Molecular Docking: Identification of Key Molecular Targets.International journal of molecular sciences · 2025Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Obesity is associated with the gut microbiome. Here, we report that gut commensal Clostridia bacteria regulate host energy balance through the tryptophan-derived metabolite indole-3-propionic acid (IPA). IPA acts as an endogenous leptin sensitiser to counteract obesity. Mechanistically, IPA is secreted from the gut into the circulation, and then targets to the STAT3 in the hypothalamic appetite regulation centre, promoting its phosphorylation and nuclear translocation, which enhances the body's response to leptin, and regulates the balance between appetite and energy metabolism. The in vitro pull-down assays involving site-directed mutagenesis demonstrate that Trp623 in the SH2 domain is the key binding site for STAT3-IPA interaction. High-fat diet (HFD), rather than genetic factors, induces excessive secretion of antimicrobial peptides by Paneth cells, inhibiting the growth of Clostridia in the gut and resulting in decreased production of the beneficial metabolite IPA. IPA or Clostridium sporogenes supplement effectively controls weight gain, improves glucose metabolism, and reduces inflammation in DIO mice. IPA fails to achieve such effects in ob/ob mice, while exogenous leptin administration restores the therapeutic effect of IPA. Our study suggests that the IPA-based gut-brain axis regulates host metabolism, and supplementation with microbiome-derived IPA could be a promising intervention strategy for treating obesity.
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