Theme park season — riding coasters I couldn't fit in before

tony_orlando 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.

anders_CPH said:

Central vs peripheral GLP-1R signaling in food noise: elegant studies using brain-penetrant vs peripherally-restricted GLP-1 agonists show that ~80%…

"Food aversion" side effect of food noise that I wasn't prepared for: I used to LOVE cooking and trying new restaurants. Now certain foods — especially red meat — literally repulse me.

It's not just reduced appetite; it's an active disgust response. My therapist says this is common and likely related to the reward pathway modulation. It's mostly a positive change, but I do miss enjoying food the way I used to.

tony_orlando 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.

Same pattern here, and in the same order.

From the other side of the consultation, briefly.

Neuroscience perspective on food noise:

GLP-1 receptors are expressed throughout the CNS, with high density in the hypothalamic arcuate nucleus, area postrema, and — critically — the mesolimbic reward pathway[1].

This is directly relevant to food noise because the central effects of GLP-1 agonists extend far beyond simple appetite suppression. The reduction in "food noise" that patients describe is likely mediated by modulation of dopaminergic signaling in the VTA and nucleus accumbens.

The emerging data on reduced addictive behaviors (alcohol, gambling) further supports this mechanism. food noise should be understood in this broader neurobiological context.