Hormonal
Long-acting GLP-1 receptor agonists (liraglutide and semaglutide) activate POMC neurons and inhibit NPY/AgRP neurons in vivo, with effects occurring 12-24 hours post-injection and dependent on the TRPC5 channel and metabolic state.
Long-acting GLP-1 drugs like liraglutide and semaglutide change brain activity related to hunger and energy use, but this happens slowly, peaking 12-24 hours after injection. This effect is stronger when you are fasting. The drug works by activating specific brain cells (POMC) that reduce hunger and inhibiting others (NPY/AgRP) that increase it, using a channel called TRPC5.
We found that liraglutide and semaglutide directly activate and increase excitatory tone to POMC neurons in a time-dependent manner... Conversely, GLP-1Ra’s decreased excitatory input to and indirectly inhibited NPY/AgRP neurons through activation of K-ATP and TRPC5 channels in GABAergic neurons. Notably, the temporal activation of POMC and inhibition of NPY/AgRP neuronal activity after liraglutide or semaglutide was injected [either intraperitoneal (I.P.) or subcutaneous (S$C.)] was dependent upon the nutritional state of the animals (fed vs food-deprived).
Why this rating
High-quality in vivo mouse models with electrophysiology and fiber photometry, though not human clinical trials.
Source
Time and metabolic state-dependent effects of GLP-1R agonists on NPY/AgRP and POMC neuronal activity in vivo
Yanbin Dong et al. · Molecular Metabolism · 2021
DOI 10.1016/j.molmet.2021.101352
Related findings · Hormonal
- Initial treatment for type 2 diabetes should be a combination of metformin and either an SGLT-2 inhibitor or a GLP-1 receptor agonist to achieve cardiorenal protection, rather than monotherapy or older agents like sulfonylureas.Strong
- For patients with specific monogenic obesity syndromes (leptin deficiency, POMC/PCSK1/LEPR mutations), targeted pharmacotherapy (recombinant leptin or setmelanotide) is highly effective and should be prioritized, unlike in polygenic obesity.Strong
- Continued weekly administration of 2.4 mg subcutaneous semaglutide prevents weight regain and promotes further weight loss in adults with overweight or obesity, whereas switching to placebo results in significant weight regain.Strong
This is one finding among thousands. Every one is graded and traced to its source, so you can see what the evidence actually supports. Browse the research →