The study aims to investigate the kinetics of the naturally occurring peptide liver-enriched antimicrobial peptide 2 (LEAP-2) in healthy volunteers. The overall objective is to investigate the physiological importance of LEAP-2 in healthy subjects.

In a recent study, the molecular phenotype of enteroendocrine cells in the small intestine before and after Roux-en-Y Gastric Bypass (RYGB) surgery in obese individuals was examined. Enteroendocrine cells were identified and isolated from intestinal biopsies and analysed for differentially expressed genes by Illumina High Throughput RNA-sequencing. It was discovered that the gene encoding liver-enriched antimicrobial peptide 2 (LEAP2), a naturally occurring peptide in humans, was significantly upregulated compared to baseline expression. Interestingly, LEAP2 was recently shown to antagonize ghrelin function in response to feeding in mice. Moreover, the mature murine LEAP2 peptide is identical in mice and humans. Thus, LEAP2 has been identified as an endogenous peptide that may be able to alter feeding behaviour and maintenance of glucose levels during calorie restriction.

This study aims to investigate the kinetics of exogenous LEAP2 in healthy subjects.

Inclusion Criteria:

• Caucasian men
• Age between 18 and 25 years
• Body mass index between 20-35 kg/m2
• Informed consent

Exclusion Criteria:

• Anaemia (haemoglobin below normal range)
• Alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) >2 times normal values) or history of hepatobiliary and/or gastrointestinal disorder(s)
• Nephropathy (serum creatinine above normal range and/or albuminuria)
• Allergy or intolerance to ingredients included in the standardised meals
• First-degree relatives with diabetes and/or glycated haemoglobin (HbA1c) >48 mmol/mol
• Regular tobacco smoking or use of other nicotine-containing products
• Any ongoing medication that the investigator evaluates would interfere with trial participation.
• Any physical or psychological condition that the investigator evaluates would interfere with trial participation including any acute or chronic illnesses