Research
Hormonal
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.
Combining oxytocin with a CCK receptor agonist is more effective for weight loss than using either drug alone. This suggests that future obesity treatments might need to target multiple pathways simultaneously to overcome diet-induced resistance.
GoodSupportsHIGH confidence
Combined OTR-CCKAR co-agonism improves metabolic outcomes in DIO mice
Why this rating
Strong mechanistic evidence using 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
- Selective activation of oxytocin-expressing PVN neurons (PVNOT) restores the ability of cholecystokinin (CCK) to suppress food intake in diet-induced obese mice.Good
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