LEAP2 mediates long-term inhibition of orexigenic neurons of the hypothalamus in mice.

LEAP2 causes a sustained inhibition of orexigenic neurons in the hypothalamus of mice, lasting several hours after pretreatment.

• Why it matters: Understanding how LEAP2 influences feeding behavior is crucial for developing therapies for obesity and metabolic disorders, as its central mechanisms remain unclear.
• What they did: The study used in vivo, ex vivo, and in vitro approaches with male mice to show that circulating LEAP2 accesses the arcuate nucleus, binds GHSR without internalization, and inhibits ghrelin-induced feeding and AgRP neuron activation.
• The result: LEAP2 acts as a long-lasting inhibitor of hypothalamic orexigenic centers, providing a mechanistic basis for its anorectic effects and highlighting its potential as a therapeutic target.