Sustained Weight Loss With Combined LEAP2 and Semaglutide Treatment in Mice.

ABSTRACT: The recent identification of liver-expressed antimicrobial peptide 2 (LEAP2) as an endogenous antagonist and inverse agonist of the growth hormone secretagogue receptor (GHSR) has revived interest in targeting the ghrelin-GHSR pathway for obesity treatment. Here, we assessed the preclinical efficacy of treatment with a long-acting LEAP2 (LA-LEAP2) analog for weight loss and explored its potential as an adjunct to semaglutide to enhance weight reduction and mitigate weight regain. We found that LA-LEAP2 lowered body weight in obese mice, which was reflected in reduced energy intake and preserved energy expenditure. While not uniformly observed across all experiments, some studies demonstrated superior weight reduction with the combination of LA-LEAP2 and semaglutide compared with semaglutid

SUBMITTER: Holm SK 

PROVIDER: S-EPMC12585159 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature