Obesity
Conditions
Brief summary
The study aim to delineate the effects of the naturally occurring peptide liver-enriched antimicrobial peptide 2 (LEAP-2) on postprandial glucose metabolism and food intake in healthy volunteers. The overall objective is to investigate the physiological importance of LEAP-2 in healthy subjects.
Detailed description
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 (LEAP-2), a naturally occurring peptide in humans, was significantly upregulated compared to baseline expression. Interestingly, LEAP-2 was recently shown to antagonize ghrelin function in response to feeding in mice. Moreover, the mature murine LEAP-2 peptide is identical in mice and humans. Thus, LEAP-2 has been identified as an endogenous peptide that may be able to alter feeding behaviour and maintenance of glucose levels during calorie restriction. The study hypothesis is that LEAP-2 alters postprandial glucose metabolism and decreases appetite as well as food intake in relation to a liquid mixed meal and a standardised ad libitum meal compared with saline (placebo) in healthy subjects.
Interventions
BIOLOGICALLiver-enriched antimicrobial peptide 2
IV infusion of LEAP2, approximately 5 hours
BIOLOGICALPlacebo
IV infusion of saline, approximately 5 hours
Sponsors
University Hospital, Gentofte, Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Day A and B will be conducted in a randomised, double-blinded order (blinded for the participant and the investigator) and noted by a third person not participating in the collection or analyses of data. The infusion order will be opened after the primary data analyses.
Intervention model description
The study is designed as a clinical, placebo-controlled, double-blinded cross-over study involving two experimental study days.
Eligibility
Sex/Gender
MALE
Age
18 Years to 25 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Food intake | 260 to 290 minutes | Difference in food intake during an ad libitum meal. Food intake is examined as kilojoules (kJ) and kJ/kg body weight of food eaten during the ad libitum meal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Alterations in gastric emptying | -30 to 290 minutes | Paracetamol concentration in plasma after intake of 1.5 g paracetamol |
| Plasma insulin levels and beta cell secretion assessed by plasma C-peptide concentration relative to plasma glucose concentration | -30 to 290 minutes | Plasma insulin levels and beta cell secretion assessed by plasma C-peptide concentration relative to plasma glucose concentration |
| Plasma/serum concentrations of LEAP-2, acyl-ghrelin as well as other glucose- and appetite-regulating gut hormones | -30 to 290 minutes | Plasma/serum concentrations of LEAP-2, acyl-ghrelin as well as other glucose- and appetite-regulating gut hormones |
| Changes in resting energy expenditure (REE) | -30 to 290 minutes | Changes in resting energy expenditure (REE) measured by indirect calorimetry |
| VAS | -30 to 290 minutes | Visual analogue scales (VASs) assessing appetite, satiety and hunger sensations (from 0 to 10 cm on a scale = from mimimum to maximum sensation) |
| Triglyceride responses | -30 to 290 minutes | Plasma triglyceride |
| Cholesterol responses | -30 to 290 minutes | Plasma cholesterol |
| Free fatty acid responses | -30 to 290 minutes | Plasma free fatty acid |
| Assessment of nitrogen balance and protein breakdown in urine | -30 to 290 minutes | Urine concentrations of urea for assessment of nitrogen balance and protein breakdown |
Countries
Denmark
Outcome results
None listed