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

Christoffer A. Hagemann; Malene S. Jensen; Stephanie Holm; Lærke S. Gasbjerg; Sarah Byberg; Kirsa Skov-Jeppesen; Bolette Hartmann; Jens J. Holst; Flemming Dela; Tina Vilsbøll; Mikkel B. Christensen; Birgitte Holst; Filip K. Knop

doi:10.1016/j.xcrm.2022.100582

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

Christoffer A. Hagemann, Malene S. Jensen, Stephanie Holm, Lærke S. Gasbjerg, Sarah Byberg, Kirsa Skov-Jeppesen, Bolette Hartmann, Jens J. Holst, Flemming Dela, Tina Vilsbøll, Mikkel B. Christensen, Birgitte Holst (Corresponding Author), Filip K. Knop (Corresponding Author)

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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.

Original language	English
Article number	100582
Number of pages	17
Journal	Cell Reports Medicine
Volume	3
Issue number	4
DOIs	https://doi.org/10.1016/j.xcrm.2022.100582
Publication status	Published - 19 Apr 2022
Externally published	Yes

Keywords*

clinical trial
food intake
glucose metabolism
growth hormone secretagogue receptor
liver-expressed antimicrobial peptide 2

Field of Science*

3.1 Basic medicine
1.6 Biological sciences

Publication Type*

1.1. Scientific article indexed in Web of Science and/or Scopus database

Access to Document

10.1016/j.xcrm.2022.100582Licence: CC BY

LEAP2 reduces postprandial glucose excursionsFinal published version, 2.55 MBLicence: CC BY

Cite this

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, 3(4), Article 100582. https://doi.org/10.1016/j.xcrm.2022.100582

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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.",

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author = "Hagemann, {Christoffer A.} and Jensen, {Malene S.} and Stephanie Holm and Gasbjerg, {L{\ae}rke S.} and Sarah Byberg and Kirsa Skov-Jeppesen and Bolette Hartmann and Holst, {Jens J.} and Flemming Dela and Tina Vilsb{\o}ll and Christensen, {Mikkel B.} and Birgitte Holst and Knop, {Filip K.}",

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day = "19",

doi = "10.1016/j.xcrm.2022.100582",

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AU - Hagemann, Christoffer A.

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AU - Holm, Stephanie

AU - Gasbjerg, Lærke S.

AU - Byberg, Sarah

AU - Skov-Jeppesen, Kirsa

AU - Hartmann, Bolette

AU - Holst, Jens J.

AU - Dela, Flemming

AU - Vilsbøll, Tina

AU - Christensen, Mikkel B.

AU - Holst, Birgitte

AU - Knop, Filip K.

PY - 2022/4/19

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AB - 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.

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

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