Research
Hormonal
Selective activation of oxytocin-expressing PVN neurons (PVNOT) restores the ability of cholecystokinin (CCK) to suppress food intake in diet-induced obese mice.
This finding suggests that simply taking CCK might not work for obese individuals because their oxytocin pathway is disconnected. Future therapies might need to combine CCK with agents that activate oxytocin neurons or bypass this block to be effective.
GoodSupportsHIGH confidence
Restoration of OT-CCK signaling rescues the suppression of feeding
Why this rating
Strong mechanistic evidence using chemogenetics and polypharmacology in mouse models.
Source
High-calorie diets uncouple hypothalamic oxytocin neurons from a gut-to-brain satiation pathway via κ-opioid signaling
Tim Gruber et al. · Cell Reports · 2023
DOI 10.1016/j.celrep.2023.113305
mechanism_onlyCited 23×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- High-calorie diets uncouple hypothalamic oxytocin (PVNOT) neurons from gut-derived CCK signaling via increased kappa-opioid tone and reduced CCKAR expression, rendering CCK ineffective at suppressing food intake.Good
- Combined pharmacological administration of oxytocin (OT) and a selective CCKAR agonist (A-71263) produces greater weight loss and fat mass reduction than either agent alone in diet-induced obese mice.Good
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