Metabolic & Cardiometabolic · Gut & Microbiome
Does gut inflammation blunt the appetite hormone GLP-1?
The claim, precisely: metabolic endotoxemia (LPS) causes GLP-1 resistance
Contested Metabolic & Cardiometabolic 🐭 Non-human evidence🔬 Includes disconfirming
RefutedContestedStrong support
consensus score 0.16
Unclear — evidence is mixed, and almost all of it is in animals or the lab so far.
Evidence ladder
How far up the ladder this claim has climbed. A high consensus on a low rung means "consistent so far," not "proven in people."
Top evidence so far: Animal studies (Animal)
MechanismIn-vitroAnimalObservationalRCTMeta-analysis
How the studies fall
4 support 2 contradict 0 tested null 0 mixed · 5 sources, 5 independent groups
What the evidence shows
Inflammation/LPS blunts GLP-1 signaling two ways: impaired FXR/TGR5-mediated secretion, and GLP-1-RECEPTOR silencing via promoter hypermethylation (DNMT3A/3B). 'GLP-1 resistance' is ligand- and receptor-side. Animal/mechanism-grade.
The evidence (6)
| Source | Grade | Stance | Quality | Finding |
|---|---|---|---|---|
| Deng et al. 2026 · Biochem Pharmacol | in-vitro | supports | moderate | [FT-verified] LPS->DNMT3->GLP-1R promoter hypermethylation->reduced receptor (resistance mechanism) ⚠️ correction-on-file (Crossref) - kept, corrigendum not retraction |
| Deng et al. 2026 · Biochem Pharmacol | animal | supports | moderate | LPS -> DNMT3A/3B -> GLP-1R promoter hypermethylation -> receptor silencing; restoring GLP-1R rescued response ⚠️ correction-on-file (Crossref) - kept, corrigendum not retraction |
| Long et al. 2026 · Front Endocrinol | mechanism | supports | low | Endotoxemia -> impaired FXR/TGR5-mediated GLP-1 secretion (gut-immune-metabolic axis) |
| Nakamori 2024 · J Physiol | animal | contradicts | moderate | Luminal LPS stimulates GLP-1 release from colonic L cells via TLR4 (LPS raises, not blunts, GLP-1) |
| Lebrun 2017 · Cell Rep | animal | contradicts | moderate | [FT-verified] acute LPS RAISES GLP-1 via TLR4 (mice+humans) - opposite of secretory resistance |
| Zong 2022 · Int J Mol Sci | animal | supports | moderate | Salmonella/endotoxin lowers blood GLP-1 by triggering enteroendocrine L-cell pyroptosis |
Educational only, not medical advice. Grades and scores reflect published evidence weighted by study design and quality; see the methodology.