Nutrient sensing:: LEAP2 concentration in response to fasting, glucose, lactate, and β-hydroxybutyrate in healthy young males

Mette Glavind Bülow Pedersen; Esben Stistrup Lauritzen; Mads Vandsted Svart; Julie Støy; Esben Søndergaard; Henrik Holm Thomsen; Ulla Kampmann; Mette Bjerre; Niels Jessen; Niels Møller; Nikolaj Rittig

doi:10.1016/j.ajcnut.2023.10.007

Nutrient sensing: LEAP2 concentration in response to fasting, glucose, lactate, and β-hydroxybutyrate in healthy young males

Mette Glavind Bülow Pedersen^*, Esben Stistrup Lauritzen, Mads Vandsted Svart, Julie Støy, Esben Søndergaard, Henrik Holm Thomsen, Ulla Kampmann, Mette Bjerre, Niels Jessen, Niels Møller, Nikolaj Rittig

^*Corresponding author for this work

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Abstract

BACKGROUND: The appetite-suppressing potential of liver-expressed antimicrobial peptide 2 (LEAP2), and its antagonistic effects on the hunger-inducing hormone ghrelin have attracted scientific interest. It is unclear how LEAP2 is influenced by fasting and how it responds to specific nutrients.

OBJECTIVES: The purpose of this investigation was to assess whether LEAP2 concentration 1) decreases after fasting, 2) increases postprandially, and 3) is regulated by nutrient sensing in the splanchnic bed.

METHODS: Plasma LEAP2 concentration was measured in blood samples from 5 clinical cross-over trials, following 1) 36 h of fasting (n = 8), 2) 10 h of fasting (n = 37, baseline data pooled from 4 of the clinical trials), 3) Oral and intravenous glucose administration (n = 11), 4) Oral and intravenous Na-lactate administration (n = 10), and 5) Oral and intravenous Na-β-hydroxybutyrate (BHB) administration (n = 8). All 5 trials included healthy males.

RESULTS: Compared with a 10-h fasting period, the median LEAP2 concentration was 38% lower following 36 h of fasting (P < 0.001). Oral administration of glucose elevated, whereas intravenous glucose administration lowered LEAP2 concentration (intervention x time, P = 0.001), resulting in a mean difference of 9 ng/mL (95% confidence interval [CI]: 1, 17) after 120 min. Oral lactate increased, and intravenous lactate decreased LEAP2 (intervention x time, P = 0.007), with a mean difference between interventions of 10 ng/mL (95% CI: 6, 15) after 120 min. In contrast, oral and intravenous administration of BHB reduced the LEAP2 concentration (main effect of time, P < 0.001).

CONCLUSIONS: Our investigations show that LEAP2 concentration was lower after a 36-h fast than an overnight fast and that oral delivery of glucose and lactate elevated LEAP2 concentration compared with intravenous administration, whereas LEAP2 concentrations decreased with both oral and intravenous BHB. This indicates that the LEAP2 concentration is sensitive to intestinal exposure to specific substrates, highlighting the need for future studies exploring the relationship between nutrients and LEAP2. This trial was registered at clinicaltrials.gov as NCT01840098, NCT03204877, NCT04299815, NCT03935841, and NCT01705782.

Original language	English
Journal	American Journal of Clinical Nutrition
Volume	118
Issue	6
Pages (from-to)	1091-1098
Number of pages	8
ISSN	0002-9165
DOIs	https://doi.org/10.1016/j.ajcnut.2023.10.007
Publication status	Published - Dec 2023

Keywords

appetite
ghrelin
ketones
lactate
LEAP2
Fasting
Lactic Acid
Humans
Male
Glucose
3-Hydroxybutyric Acid
Hunger
Ghrelin

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10.1016/j.ajcnut.2023.10.007

1-s2.0-S0002916523661817-mainFinal published version, 1.32 MBLicence: CC BY

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Pedersen, M. G. B., Lauritzen, E. S., Svart, M. V., Støy, J., Søndergaard, E., Thomsen, H. H., Kampmann, U., Bjerre, M., Jessen, N., Møller, N., & Rittig, N. (2023). Nutrient sensing: LEAP2 concentration in response to fasting, glucose, lactate, and β-hydroxybutyrate in healthy young males. American Journal of Clinical Nutrition, 118(6), 1091-1098. https://doi.org/10.1016/j.ajcnut.2023.10.007

@article{b8223b7df34f4a309e659e314cdbaaa7,

title = "Nutrient sensing:: LEAP2 concentration in response to fasting, glucose, lactate, and β-hydroxybutyrate in healthy young males",

abstract = "BACKGROUND: The appetite-suppressing potential of liver-expressed antimicrobial peptide 2 (LEAP2), and its antagonistic effects on the hunger-inducing hormone ghrelin have attracted scientific interest. It is unclear how LEAP2 is influenced by fasting and how it responds to specific nutrients.OBJECTIVES: The purpose of this investigation was to assess whether LEAP2 concentration 1) decreases after fasting, 2) increases postprandially, and 3) is regulated by nutrient sensing in the splanchnic bed.METHODS: Plasma LEAP2 concentration was measured in blood samples from 5 clinical cross-over trials, following 1) 36 h of fasting (n = 8), 2) 10 h of fasting (n = 37, baseline data pooled from 4 of the clinical trials), 3) Oral and intravenous glucose administration (n = 11), 4) Oral and intravenous Na-lactate administration (n = 10), and 5) Oral and intravenous Na-β-hydroxybutyrate (BHB) administration (n = 8). All 5 trials included healthy males.RESULTS: Compared with a 10-h fasting period, the median LEAP2 concentration was 38% lower following 36 h of fasting (P < 0.001). Oral administration of glucose elevated, whereas intravenous glucose administration lowered LEAP2 concentration (intervention x time, P = 0.001), resulting in a mean difference of 9 ng/mL (95% confidence interval [CI]: 1, 17) after 120 min. Oral lactate increased, and intravenous lactate decreased LEAP2 (intervention x time, P = 0.007), with a mean difference between interventions of 10 ng/mL (95% CI: 6, 15) after 120 min. In contrast, oral and intravenous administration of BHB reduced the LEAP2 concentration (main effect of time, P < 0.001).CONCLUSIONS: Our investigations show that LEAP2 concentration was lower after a 36-h fast than an overnight fast and that oral delivery of glucose and lactate elevated LEAP2 concentration compared with intravenous administration, whereas LEAP2 concentrations decreased with both oral and intravenous BHB. This indicates that the LEAP2 concentration is sensitive to intestinal exposure to specific substrates, highlighting the need for future studies exploring the relationship between nutrients and LEAP2. This trial was registered at clinicaltrials.gov as NCT01840098, NCT03204877, NCT04299815, NCT03935841, and NCT01705782.",

keywords = "appetite, ghrelin, ketones, lactate, LEAP2, Fasting, Lactic Acid, Humans, Male, Glucose, 3-Hydroxybutyric Acid, Hunger, Ghrelin",

author = "Pedersen, {Mette Glavind B{\"u}low} and Lauritzen, {Esben Stistrup} and Svart, {Mads Vandsted} and Julie St{\o}y and Esben S{\o}ndergaard and Thomsen, {Henrik Holm} and Ulla Kampmann and Mette Bjerre and Niels Jessen and Niels M{\o}ller and Nikolaj Rittig",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

month = dec,

doi = "10.1016/j.ajcnut.2023.10.007",

language = "English",

volume = "118",

pages = "1091--1098",

journal = "American Journal of Clinical Nutrition",

issn = "0002-9165",

publisher = "Elsevier B.V.",

number = "6",

}

Pedersen, MGB , Lauritzen, ES , Svart, MV , Støy, J , Søndergaard, E , Thomsen, HH, Kampmann, U, Bjerre, M , Jessen, N , Møller, N & Rittig, N 2023, 'Nutrient sensing: LEAP2 concentration in response to fasting, glucose, lactate, and β-hydroxybutyrate in healthy young males', American Journal of Clinical Nutrition, vol. 118, no. 6, pp. 1091-1098. https://doi.org/10.1016/j.ajcnut.2023.10.007

Nutrient sensing: LEAP2 concentration in response to fasting, glucose, lactate, and β-hydroxybutyrate in healthy young males. / Pedersen, Mette Glavind Bülow ; Lauritzen, Esben Stistrup ; Svart, Mads Vandsted et al.
In: American Journal of Clinical Nutrition, Vol. 118, No. 6, 12.2023, p. 1091-1098.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Nutrient sensing:

T2 - LEAP2 concentration in response to fasting, glucose, lactate, and β-hydroxybutyrate in healthy young males

AU - Pedersen, Mette Glavind Bülow

AU - Lauritzen, Esben Stistrup

AU - Svart, Mads Vandsted

AU - Støy, Julie

AU - Søndergaard, Esben

AU - Thomsen, Henrik Holm

AU - Kampmann, Ulla

AU - Bjerre, Mette

AU - Jessen, Niels

AU - Møller, Niels

AU - Rittig, Nikolaj

PY - 2023/12

Y1 - 2023/12

N2 - BACKGROUND: The appetite-suppressing potential of liver-expressed antimicrobial peptide 2 (LEAP2), and its antagonistic effects on the hunger-inducing hormone ghrelin have attracted scientific interest. It is unclear how LEAP2 is influenced by fasting and how it responds to specific nutrients.OBJECTIVES: The purpose of this investigation was to assess whether LEAP2 concentration 1) decreases after fasting, 2) increases postprandially, and 3) is regulated by nutrient sensing in the splanchnic bed.METHODS: Plasma LEAP2 concentration was measured in blood samples from 5 clinical cross-over trials, following 1) 36 h of fasting (n = 8), 2) 10 h of fasting (n = 37, baseline data pooled from 4 of the clinical trials), 3) Oral and intravenous glucose administration (n = 11), 4) Oral and intravenous Na-lactate administration (n = 10), and 5) Oral and intravenous Na-β-hydroxybutyrate (BHB) administration (n = 8). All 5 trials included healthy males.RESULTS: Compared with a 10-h fasting period, the median LEAP2 concentration was 38% lower following 36 h of fasting (P < 0.001). Oral administration of glucose elevated, whereas intravenous glucose administration lowered LEAP2 concentration (intervention x time, P = 0.001), resulting in a mean difference of 9 ng/mL (95% confidence interval [CI]: 1, 17) after 120 min. Oral lactate increased, and intravenous lactate decreased LEAP2 (intervention x time, P = 0.007), with a mean difference between interventions of 10 ng/mL (95% CI: 6, 15) after 120 min. In contrast, oral and intravenous administration of BHB reduced the LEAP2 concentration (main effect of time, P < 0.001).CONCLUSIONS: Our investigations show that LEAP2 concentration was lower after a 36-h fast than an overnight fast and that oral delivery of glucose and lactate elevated LEAP2 concentration compared with intravenous administration, whereas LEAP2 concentrations decreased with both oral and intravenous BHB. This indicates that the LEAP2 concentration is sensitive to intestinal exposure to specific substrates, highlighting the need for future studies exploring the relationship between nutrients and LEAP2. This trial was registered at clinicaltrials.gov as NCT01840098, NCT03204877, NCT04299815, NCT03935841, and NCT01705782.

AB - BACKGROUND: The appetite-suppressing potential of liver-expressed antimicrobial peptide 2 (LEAP2), and its antagonistic effects on the hunger-inducing hormone ghrelin have attracted scientific interest. It is unclear how LEAP2 is influenced by fasting and how it responds to specific nutrients.OBJECTIVES: The purpose of this investigation was to assess whether LEAP2 concentration 1) decreases after fasting, 2) increases postprandially, and 3) is regulated by nutrient sensing in the splanchnic bed.METHODS: Plasma LEAP2 concentration was measured in blood samples from 5 clinical cross-over trials, following 1) 36 h of fasting (n = 8), 2) 10 h of fasting (n = 37, baseline data pooled from 4 of the clinical trials), 3) Oral and intravenous glucose administration (n = 11), 4) Oral and intravenous Na-lactate administration (n = 10), and 5) Oral and intravenous Na-β-hydroxybutyrate (BHB) administration (n = 8). All 5 trials included healthy males.RESULTS: Compared with a 10-h fasting period, the median LEAP2 concentration was 38% lower following 36 h of fasting (P < 0.001). Oral administration of glucose elevated, whereas intravenous glucose administration lowered LEAP2 concentration (intervention x time, P = 0.001), resulting in a mean difference of 9 ng/mL (95% confidence interval [CI]: 1, 17) after 120 min. Oral lactate increased, and intravenous lactate decreased LEAP2 (intervention x time, P = 0.007), with a mean difference between interventions of 10 ng/mL (95% CI: 6, 15) after 120 min. In contrast, oral and intravenous administration of BHB reduced the LEAP2 concentration (main effect of time, P < 0.001).CONCLUSIONS: Our investigations show that LEAP2 concentration was lower after a 36-h fast than an overnight fast and that oral delivery of glucose and lactate elevated LEAP2 concentration compared with intravenous administration, whereas LEAP2 concentrations decreased with both oral and intravenous BHB. This indicates that the LEAP2 concentration is sensitive to intestinal exposure to specific substrates, highlighting the need for future studies exploring the relationship between nutrients and LEAP2. This trial was registered at clinicaltrials.gov as NCT01840098, NCT03204877, NCT04299815, NCT03935841, and NCT01705782.

KW - appetite

KW - ghrelin

KW - ketones

KW - lactate

KW - LEAP2

KW - Fasting

KW - Lactic Acid

KW - Humans

KW - Male

KW - Glucose

KW - 3-Hydroxybutyric Acid

KW - Hunger

KW - Ghrelin

UR - http://www.scopus.com/inward/record.url?scp=85175627997&partnerID=8YFLogxK

U2 - 10.1016/j.ajcnut.2023.10.007

DO - 10.1016/j.ajcnut.2023.10.007

M3 - Journal article

C2 - 37844838

AN - SCOPUS:85175627997

SN - 0002-9165

VL - 118

SP - 1091

EP - 1098

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

IS - 6

ER -

Nutrient sensing: LEAP2 concentration in response to fasting, glucose, lactate, and β-hydroxybutyrate in healthy young males

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