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

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 in...

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Published in:Cell reports. Medicine 2022-04, Vol.3 (4), p.100582-100582, Article 100582
Main Authors: Hagemann, Christoffer A., Jensen, Malene S., Holm, Stephanie, Gasbjerg, Lærke S., Byberg, Sarah, Skov-Jeppesen, Kirsa, Hartmann, Bolette, Holst, Jens J., Dela, Flemming, Vilsbøll, Tina, Christensen, Mikkel B., Holst, Birgitte, Knop, Filip K.
Format: Article
Language:English
Subjects:
Animals
Blood Glucose
clinical trial
Eating
food intake
Ghrelin
Glucose - pharmacology
glucose metabolism
growth hormone secretagogue receptor
Humans
liver-expressed antimicrobial peptide 2
Mice
Receptors, Ghrelin
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Summary: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. [Display omitted] •Exogenous LEAP2 lowers postprandial plasma glucose excursions•Exogenous LEAP2 suppresses ad libitum food intake•During fasting, exogenous LEAP2 increases insulin secretion and suppresses lipolysis•The GHSR is required for eliciting LEAP2 effects in mice LEAP2 was recently discovered as a hormone in rodents, which modulates ghrelin actions on plasma glucose and appetite. In a randomized, double-blind, placebo-controlled trial, Hagemann et al. demonstrate that exogenous LEAP2 reduces postprandial glucose excursions and food intake in healthy men.
ISSN:2666-3791
2666-3791
DOI:10.1016/j.xcrm.2022.100582