Hormonal
Peripheral administration of the GLP-1 receptor agonist liraglutide induces weight loss primarily by crossing the blood-brain barrier to activate GLP-1 receptors on POMC/CART neurons in the arcuate nucleus (ARC), rather than via vagal or area postrema pathways.
Liraglutide reduces body weight by entering the brain and activating specific neurons (POMC/CART) in the arcuate nucleus that regulate appetite. This central action is the primary driver of weight loss, distinct from peripheral effects like slowed stomach emptying. The drug requires crossing the blood-brain barrier to bind to GLP-1 receptors on these specific neurons.
Collectively, our findings indicate that the GLP-1R on POMC/CART-expressing ARC neurons likely mediates liraglutide-induced weight loss.
Why this rating
High-quality animal models with rigorous lesioning, genetic knockout, and electrophysiological validation, though not human clinical trials.
Source
The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss
Anna Secher et al. · Journal of Clinical Investigation · 2014
DOI 10.1172/jci75276
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