The food noise came back three weeks after I reduced my dose, well before the weight moved, which tells me something about which effect tracks what.
The bit I cannot resolve on my own is whether the quiet is the same mechanism as the appetite suppression or a separate one, because they seem to come and go on different schedules.
If the honest answer is that nobody knows, that is a useful answer and I would rather have it.
AussieAnna said:The food noise came back three weeks after I reduced my dose, well before the weight moved, which tells me something about which effect tracks what.
Central vs peripheral GLP-1R signaling in food noise: elegant studies using brain-penetrant vs peripherally-restricted GLP-1 agonists show that ~80% of the weight loss effect is centrally mediated[1].
The key brain regions: arcuate nucleus (appetite), area postrema (nausea), NTS (satiety), VTA/NAc (reward). Peripheral effects (gastric emptying, insulin secretion) contribute but are secondary for weight loss.
This has implications for next-gen drugs: optimizing brain penetration and CNS receptor occupancy may be more important than systemic exposure.
[1] Secher A, et al. J Clin Invest. 2014;124(10):4473-4488.
JennaRN said:Central vs peripheral GLP-1R signaling in food noise: elegant studies using brain-penetrant vs peripherally-restricted GLP-1 agonists show that ~80%…
JennaRN said:...regarding food noise mechanism of action...
To build on this — the mechanism is more complex than "it makes you less hungry." GLP-1 agonists:
- Activate hypothalamic satiety centers (appetite reduction)
- Delay gastric emptying (prolonged fullness)
- Potentiate glucose-dependent insulin secretion
- Suppress glucagon secretion
- Modulate reward pathway dopaminergic signaling
- Reduce hepatic lipogenesis
- Have direct cardiovascular protective effects
It's a multi-target drug with systemic metabolic effects. Understanding the mechanism helps us predict and manage side effects.
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Browse GL BiochemAussieAnna said:The food noise came back three weeks after I reduced my dose, well before the weight moved, which tells me something about which effect tracks what.
Second this. I had assumed I was the exception until I read this.
From the other side of the consultation, briefly.
The GLP-1 and alcohol use disorder connection, relevant to food noise: observational data from Scandinavian registries shows reduced alcohol-related hospitalizations in GLP-1 agonist users[1].
The mechanism is plausible: GLP-1R is expressed in the mesolimbic reward pathway (VTA, nucleus accumbens). Agonism at these receptors may reduce the reinforcing properties of alcohol, similar to the reduction in "food noise."
RCTs for GLP-1 agonists in AUD are now underway. If positive, this would be a paradigm-shifting repurposing of existing medications.
[1] Wang W, et al. Nat Med. 2024;30:574-584.