LEAP2 on Postprandial Glucose Metabolism and Food Intake n Obese Males
- Conditions
- Obesity
- Interventions
- Drug: LEAP-2 Protein, Human
- Registration Number
- NCT05603598
- Lead Sponsor
- University Hospital, Gentofte, Copenhagen
- Brief Summary
The study aims to delineate the effects of the naturally occurring peptide liver-enriched antimicrobial peptide 2 (LEAP-2) on postprandial glucose metabolism and food intake in obese volunteers. The overall objective is to investigate the physiological importance of LEAP-2 in obese 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. Our group recently found a 12 % relative reduction in ad libitum food intake and reduced postprandial glucose excursions.
The present 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 obese subjects.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 20
- Caucasian men
- Age between 18 and 25 years
- Body mass index between 30-50 kg/m2
- Informed consent
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Placebo LEAP-2 Protein, Human IV infusion of saline, approximately 5.5 hours Liver-enriched antimicrobial peptide 2 LEAP-2 Protein, Human IV infusion of LEAP2, approximately 5.5 hours
- Primary Outcome Measures
Name Time Method Food intake, kilojoules per kilogram body weight 290 to 320 minutes Difference in food intake during an ad libitum meal. Food intake is examined as kilojoules per kilogram body weight of food eaten during the ad libitum meal.
Food intake, kilojoules 290 to 320 minutes Difference in food intake during an ad libitum meal. Food intake is examined as kilojoules of food eaten during the ad libitum meal.
- Secondary Outcome Measures
Name Time Method VAS, appetite -35 to 320 minutes Visual analogue scales (VASs) assessing appetite (from 0 to 9,5 cm on a scale = from minimum to maximum sensation)
VAS, satiety -35 to 320 minutes Visual analogue scales (VASs) assessing satiety sensations (from 0 to 9,5 cm on a scale = from minimum to maximum sensation)
VAS, hunger -35 to 320 minutes Visual analogue scales (VASs) assessing hunger sensations (from 0 to 9,5 cm on a scale = from minimum to maximum sensation)
VAS, thirst -35 to 320 minutes Visual analogue scales (VASs) assessing thirst (from 0 to 9,5 cm on a scale = from minimum to maximum sensation)
Alterations in gastric emptying -35 to 320 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 -35 to 320 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 -35 to 320 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) -35 to 320 minutes Changes in resting energy expenditure (REE) measured by indirect calorimetry
Triglyceride responses -35 to 320 minutes Plasma triglyceride
Cholesterol responses -35 to 320 minutes Plasma Cholesterol
Free fatty acid responses -35 to 320 minutes Plasma Free fatty acid
Trial Locations
- Locations (1)
Center for Clinical Metabolic Research, Gentofte Hospital
🇩🇰Hellerup, Capital Region, Denmark