Hormonal
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.
If you are eating a high-calorie, high-fat/sugar diet, your body's natural ability to feel full from gut hormones like CCK is biologically suppressed. This is not a failure of willpower but a broken signal. To regain control, you must address the diet composition to potentially restore this pathway, or utilize interventions (like specific pharmacological combinations of OT and CCKAR agonists shown in the study) that bypass this block.
High-calorie diets uncouple hypothalamic oxytocin neurons from a gut-to-brain satiation pathway via k-opioid signaling
Why this rating
High-quality mechanistic evidence using multiple mouse models (ablation, chemogenetics, snRNA-seq, patch-clamp), though translational to humans is not explicitly tested.
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
More from this paper
- Selective activation of oxytocin-expressing PVN neurons (PVNOT) restores the ability of cholecystokinin (CCK) to suppress food intake in diet-induced obese mice.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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