LEAP2 reduces postprandial glucose excursions and ad libitum food intake in healthy men

Abstract

The gastric hormone ghrelin stimulates food intake and increases plasma glucose through activation of the growth hormone secretagogue receptor (GHSR). Liver-expressed antimicrobial peptide 2 (LEAP2) has been proposed to inhibit actions of ghrelin through inverse effects on GHSR activity. Here, we investigate the effects of exogenous LEAP2 on postprandial glucose metabolism and ad libitum food intake in a randomized, double-blind, placebo-controlled, crossover trial of 20 healthy men. We report that LEAP2 infusion lowers postprandial plasma glucose and growth hormone concentrations and decreases food intake during an ad libitum meal test. In wild-type mice, plasma glucose and food intake are reduced by LEAP2 dosing, but not in GHSR-null mice, pointing to GHSR as a potential mediator of LEAP2's glucoregulatory and appetite-suppressing effects in mice.

Description

Publisher Copyright: © 2022 The Author(s)

Keywords

clinical trial, food intake, glucose metabolism, growth hormone secretagogue receptor, liver-expressed antimicrobial peptide 2, 3.1 Basic medicine, 1.6 Biological sciences, 1.1. Scientific article indexed in Web of Science and/or Scopus database, General Biochemistry,Genetics and Molecular Biology

Citation

Hagemann, C A, Jensen, M S, Holm, S, Gasbjerg, L S, Byberg, S, Skov-Jeppesen, K, Hartmann, B, Holst, J J, Dela, F, Vilsbøll, T, Christensen, M B, Holst, B & Knop, F K 2022, 'LEAP2 reduces postprandial glucose excursions and ad libitum food intake in healthy men', Cell Reports Medicine, vol. 3, no. 4, 100582. https://doi.org/10.1016/j.xcrm.2022.100582