The Journal of clinical investigation

The brain's appetite control center helps liraglutide cause weight loss

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated

Abstract

Liraglutide binding in the brain requires the GLP-1 receptor, as shown by the absence of binding in Glp1r(-/-) mice.

  • Liraglutide does not activate GLP-1-producing neurons in the hindbrain.
  • Weight reduction from liraglutide in rats is independent of GLP-1 receptors in key brain areas.
  • Fluorescently labeled liraglutide was found in the brain's circumventricular organs and bound to neurons in the arcuate nucleus.
  • Liraglutide is internalized in neurons expressing proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) in the arcuate nucleus.
  • Electrophysiological studies indicate that GLP-1 directly stimulates POMC/CART neurons and inhibits neuropeptide Y (NPY) and agouti-related peptide (AgRP) neurons.

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