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Pre-prandial plasma liver-expressed antimicrobial peptide 2 (LEAP2) concentration in humans is inversely associated with hunger sensation in a ghrelin independent manner

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European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

The liver-expressed antimicrobial peptide 2 (LEAP2) is a newly recognized peptide hormone that acts via the growth hormone secretagogue receptor (GHSR) blunting the effects of ghrelin and displaying ghrelin-independent actions. Since the implications of LEAP2 are beginning to be elucidated, we investigated if plasma LEAP2 concentration varies with feeding status or sex and whether it is associated with glucose metabolism and appetite sensations.

Methods

We performed a single test meal study, in which plasma concentrations of LEAP2, ghrelin, insulin and glucose as well as visual analogue scales for hunger, desire to eat, prospective food consumption, fullness were assessed before and 60 min after breakfast in 44 participants (n = 21 females) with normal weight (NW) or overweight/obesity (OW/OB).

Results

Pre-prandial plasma LEAP2 concentration was ~ 1.6-fold higher whereas ghrelin was ~ 2.0-fold lower in individuals with OW/OB (p < 0.001) independently of sex. After adjusting for body mass index (BMI) and sex, pre-prandial plasma LEAP2 concentration displayed a direct relationship with BMI (β: 0.09; 95%CI: 0.05, 0.13; p < 0.001), fat mass (β: 0.05; 95%CI: 0.01, 0.09; p = 0.010) and glycemia (β: 0.24; 95%CI: 0.05, 0.43; p = 0.021), whereas plasma ghrelin concentration displayed an inverse relationship with BMI and fat mass but not with glycemia. Postprandial plasma LEAP2 concentration increased ~ 58% in females with OW/OB (p = 0.045) but not in females with NW or in males. Pre-prandial plasma LEAP2 concentration displayed an inverse relationship with hunger score (β: − 11.16; 95% CI: − 18.52, − 3.79; p = 0.004), in a BMI-, sex- and ghrelin-independent manner.

Conclusions

LEAP2 emerges as a key hormone implicated in the regulation of metabolism and appetite in humans.

Trial registration

The study was retrospectively registered in clinicaltrials.gov (April 2023). ClinicalTrials.gov Identifier: NCT05815641.

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Data availability

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation, to any qualified researcher.

Abbreviations

ANOVA:

Analysis of variance

AUC:

Area under the curve

BMI:

Body mass index

GHSR:

Growth hormone secretagogue receptor

HOMA:

Homeostasis model assessment for insulin resistance

IQR:

Interquartile range

LEAP2:

Liver-expressed antimicrobial peptide 2

NW:

Normal weight

OB:

Obesity

OW:

Overweight

VAS:

Visual analogue scales

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Acknowledgements

We thank to all the participants of the study, to the deputy director of the Instituto Biológico (Dr. H. Giudicci), who kindly allowed the use of the facilities to perform the studies, and to Camila Saenz and Ana Luz Kruger for their technical assistance.

Funding

This work was supported by grants from Fondo para la Investigación Científica y Tecnológica (FONCyT, PICT2017-3196, PICT2019-3054 and PICT2020-3270 to MP; PICT2019-256 to MFA), CONICET (PUE105 to MP), The National Qatar Research Foundation (NPRP13S-0209-200315 to AMH, MP and SAD) and Fundación Florencio Fiorini (to MFA).

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Author notes

  1. María F. Andreoli and Antonela S. Fittipaldi co-first authors.

Authors and Affiliations

  1. Instituto de Desarrollo e Investigaciones Pediátricas (IDIP), HIAEP Sor María Ludovica de la Plata, Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC-PBA), Calle 63 # 1069, La Plata, Buenos Aires, Argentina

    María F. Andreoli, Ignacio Mendez & María V. Fasano

  2. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), La Plata, Argentina

    María F. Andreoli

  3. Grupo de Neurofisiología, Instituto Multidisciplinario de Biología Celular (IMBICE). Universidad Nacional la Plata (UNLP), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) y CIC-PBA, Calle 526 S/N Entre 10 y 11, La Plata, Buenos Aires, Argentina

    Antonela S. Fittipaldi, Daniel Castrogiovanni, Pablo N. De Francesco, Spring Valdivia, Florencia Heredia & Mario Perello

  4. Bertin Technologies, Le Bretonneux, France

    Carole Ribet-Travers

  5. Centro de Matemática la Plata, Facultad de Ciencias Exactas, UNLP/CIC-PBA, La Plata, Argentina

    María V. Fasano

  6. Department of Surgical Sciences, Functional Pharmacology and Neuroscience, University of Uppsala, Uppsala, Sweden

    María F. Andreoli, Helgi B. Schioth & Mario Perello

  7. Department of Population Medicine, College of Medicine, QU Health, Qatar University, Doha, Qatar

    Suhail A. Doi

  8. College of Medicine, QU Health, Qatar University, Doha, Qatar

    Abdella M. Habib

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  1. María F. Andreoli
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Contributions

Conceptualization, formal analysis, original draft preparation, supervision, overall responsibility for the project: MFA, MP. Methodology, validation, formal analysis, investigation, resources and data curation; ASF, DC, PNDF, SV, FH, CRT, IM, MVF, HBS, SAD, FA, AMH, MFA, MP. Funding acquisition, formal analysis, reviewing and editing, supervision: AMH, SAD, MFA, MP. All authors approved the submitted and published versions.

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Correspondence to María F. Andreoli or Mario Perello.

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The authors declare no conflicts of interest. The sponsors had no role in the design of the study, the collection, analyses or interpretation of data, writing of the manuscript, or the decision to publish the results.

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Andreoli, M.F., Fittipaldi, A.S., Castrogiovanni, D. et al. Pre-prandial plasma liver-expressed antimicrobial peptide 2 (LEAP2) concentration in humans is inversely associated with hunger sensation in a ghrelin independent manner. Eur J Nutr 63, 751–762 (2024). https://doi.org/10.1007/s00394-023-03304-8

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