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. 2024 Oct;26(10):4734-4743.
doi: 10.1111/dom.15850. Epub 2024 Aug 14.

LEAP2 is associated with impulsivity and reward sensitivity depending on the nutritional status and decreases with protein intake in humans

María F Andreoli  1   2   3 , Ana Luz Kruger  1   2 , Aleksandr V Sokolov  3 , Gull Rukh  3 , Pablo N De Francesco  4 , Mario Perello  3   4 , Helgi B Schiöth  3
Affiliations

LEAP2 is associated with impulsivity and reward sensitivity depending on the nutritional status and decreases with protein intake in humans

María F Andreoli et al. Diabetes Obes Metab. 2024 Oct.

Abstract

Aim: Liver-expressed antimicrobial peptide 2 (LEAP2) dynamics in human plasma and its association with feeding behaviour remain poorly understood. Therefore, this study aims: (a) to investigate fasting LEAP2 in participants with normal weight or with overweight or mild obesity (OW/OB); (b) to study the association between fasting LEAP2 and anthropometric and metabolic traits, feeding behaviour, LEAP2 genetic variants and blood cell DNA methylation status; and (c) to ascertain postprandial changes in LEAP2 after high protein intake and the association with feeding behaviour and food intake.

Methods: Anthropometric and behavioural measures, genotyping, methylation profiling, plasma glucose and LEAP2 concentrations were assessed in 327 females and males. A subgroup of 123 participants received an ad libitum high-protein meal, and postprandial LEAP2 concentration and behavioural measures were assessed.

Results: LEAP2 concentration was higher in participants with OW/OB (p < 0.001) and in females (p < 0.001), and was associated with LEAP2 single nucleotide polymorphisms rs765760 (p = 0.012) and rs803223 (p = 0.019), but not with LEAP2 methylation status. LEAP2 concentration was directly related to glycaemia (p = 0.001) and fullness (p = 0.003) in participants with normal weight, whereas it was associated with body mass index (p = 0.018), waist circumference (p = 0.014) and motor impulsivity in participants with OW/OB (p = 0.005). A negative association with reward responsiveness was observed in participants with OW/OB (p = 0.023). LEAP2 concentration was inversely associated with food intake (p = 0.034) and decreased after a high-protein meal (p < 0.001), particularly in women (p = 0.002).

Conclusion: Increased LEAP2 in participants with OW/OB is associated with behavioural characteristics of obesity. Our results show sexual dimorphism in LEAP2 concentration before and after food intake and highlight the role of LEAP2 in feeding regulation.

Keywords: LEAP2; feeding behaviour; food intake; impulsivity; reward sensitivity.

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References

REFERENCES

    1. Ge X, Yang H, Bednarek MA, et al. LEAP2 is an endogenous antagonist of the ghrelin receptor. Cell Metab. 2018;27(2):461‐469.e6.
    1. Krause A, Sillard R, Kleemeier B, et al. Isolation and biochemical characterization of LEAP‐2, a novel blood peptide expressed in the liver. Protein Sci. 2003;12(1):143‐152.
    1. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth‐hormone‐releasing acylated peptide from stomach. Nature. 1999;402(6762):656‐660.
    1. Fernandez G, Cabral A, de Francesco PN, et al. GHSR controls food deprivation‐induced activation of CRF neurons of the hypothalamic paraventricular nucleus in a LEAP2‐dependent manner. Cell Mol Life Sci. 2022;79(5):277.
    1. Andreoli MF, De Francesco PN, Perello M. Gastrointestinal hormones controlling energy homeostasis and their potential role in obesity. In: Nillni E, ed. Textbook of Energy Balance, Neuropeptide Hormones, and Neuroendocrine Function. Springer; 2018.

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