Effects of Antagonizing the Ghrelin Receptor on Brain Food Cue Reactivity in Obesity

Effects of Antagonizing the Ghrelin Receptor on Brain Food Cue Reactivity in Obesity

The naturally occurring peptide hormone liver-expressed antimicrobial peptide 2 (LEAP2) in an antagonist/inverse agonist towards the ghrelin receptor. Ghrelin administration has previously been shown to increase food cue reactivity in brain regions related to appetite and reward using functional MRI scans.

The aim of this clinical study is to investigate the effects of LEAP2 infusion on food cue reactivity in brain regions related to appetite and reward. Since LEAP2 is an antagonist/inverse agonist towards the ghrelin receptor we hypothesize, that LEAP2 infusion will decrease food cue reactivity in the above-mentioned regions compared to placebo infusion.

Participants with obesity (BMI 30-50 kg/m2) will be included and complete two experimental days with either LEAP2 or placebo infusion in a randomized crossover manner. On experimental days, participants will undergo a MRI scan with functional and anatomical modalities.

The study will attribute to gain a deeper understanding of the ghrelin system and its interaction with appetite regulation.

Inclusion Criteria:

• Age between 18 and 60 years at the time of inclusion
• Body mass index 30-50 kg/m2
• Men
• Informed consent

Exclusion Criteria:

• Anaemia (haemoglobin below normal range)
• Alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) >2 times normal values) or present hepatobiliary and/or gastrointestinal disorder(s)
• Nephropathy (serum creatinine above normal range and/or albuminuria)
• Glycated haemoglobin (HbA1c) ≥48 mmol/mol and/or type 2 diabetes requiring medical treatment
• Regular tobacco smoking or use of other nicotine-containing products
• Claustrophobia
• 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