Hormonal
GIP receptor activation reduces the recruitment of CCKAP/NTS neurons and selectively reduces conditioned taste avoidance without abolishing weight loss.
Adding GIP receptor activation to GLP-1 therapy reduces the activation of brainstem neurons responsible for nausea, thereby reducing side effects like nausea without significantly compromising the weight-loss benefits. This suggests dual-agonists may offer a better tolerability profile.
GIP receptor activation results in a reduced recruitment of these GLP-1RA-responsive neurons and a selective reduction of conditioned taste avoidance.
Why this rating
Strong mechanistic evidence showing differential effects of GIP on CCK neurons vs other AP neurons.
Source
Anorectic and aversive effects of GLP-1 receptor agonism are mediated by brainstem cholecystokinin neurons, and modulated by GIP receptor activation
Alessia Costa et al. · Molecular Metabolism · 2021
DOI 10.1016/j.molmet.2021.101407
More from this paper
- Brainstem cholecystokinin-expressing (CCKAP/NTS) neurons are required for the appetite-suppressing and body-weight-lowering effects of GLP-1 receptor agonists.Good
- Brainstem cholecystokinin-expressing (CCKAP/NTS) neurons are necessary for GLP-1 receptor agonists to induce conditioned taste avoidance (nausea/aversive effects).Good
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