LEAP2, an antimicrobial peptide from the liver, reduces blood pressure and modulates cardiac responses to stress by blocking the ghrelin receptor.
BP reduction in normal and hypertensive ratsLEAP2 demonstrated antihypertensive effects across three experimental systems
What the researchers found
LEAP2 reduces blood pressure in both normal and hypertensive rats and modulates β-adrenergic cardiac responses, acting through GHSR antagonism and inverse agonism.
Why it matters
Discovering that an antimicrobial peptide directly regulates blood pressure opens new avenues for hypertension treatment and reveals unexpected connections between metabolism and cardiovascular function.
How the study worked
Multi-level study: in vivo (Wistar and spontaneously hypertensive rats), ex vivo (isolated hearts), and in vitro (cardiomyocytes) assessment of LEAP2 cardiovascular effects.
What this study cannot tell us
Animal study — effects in humans unknown. Acute IV administration may not reflect chronic therapeutic use. Complex interaction between GHSR constitutive activity and LEAP2 needs further characterization.
How to read the evidence
Preclinical study with multi-level validation (in vivo, ex vivo, in vitro) — strong mechanistic evidence but no human data.
When this study was published
Published in 2026; reveals a novel cardiovascular role for LEAP2.
The bigger picture
This connects the ghrelin-LEAP2 appetite axis to cardiovascular regulation, suggesting that metabolic hormones have far broader physiological roles than previously understood.
Questions still open
- Could LEAP2 or LEAP2-derived drugs be developed as novel antihypertensives?
- Does endogenous LEAP2 variation contribute to individual differences in blood pressure?
Common questions
What is LEAP2?
Could this lead to new blood pressure drugs?
Read the original research
LEAP2 modulates β-adrenergic triggered cardiac responses and provokes antihypertensive effects.
Life sciences, 390, 124243
Citation
Berrio, Sixta Isabel Atencio; Carvalho, Jhulle Horrane; Dutra, João Batista; Eliezeck, Marcos; Scalzo, Sergio; Ribeiro, Juliana Vila Verde; Mendonça, Michelle Mendanha; Gomes, Rodrigo Mello; Pedrino, Gustavo Rodrigues; Colombari, Eduardo; Castrogiovanni, Daniel; Milagros, Sisti Maria; Racioppi, Maria Florencia; Petroff, Martin Vila; Cantel, Sonia; Fehrentz, Jean-Alain; Guatimosim, Silvia; Perelló, Mario; de Castro, Carlos Henrique; Xavier, Carlos Henrique. (2026). LEAP2 modulates β-adrenergic triggered cardiac responses and provokes antihypertensive effects.. Life sciences, 390, 124243. https://doi.org/10.1016/j.lfs.2026.124243