Gut Hormone LEAP2 in Metabolism and Eating Behaviour: Fixed Meal Testing

• Male or female between the ages of 18 and 60 years;
• Without obesity with body mass index (BMI) 18.0-29.9 kg/m2 or with obesity with BMI 30.0-50.0 kg/m2;
• Healthy as determined by medical history and vital signs;
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form;
• Participant is able to read, comprehend and record information written in English.

Exclusion Criteria:

• History of, or current abuse or dependence on alcohol or drugs;
• Current smoker or less than 2 years since quitting (cigarette, cigars, e-cigarettes) or use of nicotine replacement therapy;
• Significant current or past medical or psychiatric history that, in the opinion of the investigators, contraindicates their participation;
• History of type 1 or type 2 diabetes mellitus;
• History of ischaemic heart disease, heart failure, cardiac arrhythmia, peripheral vascular, cerebrovascular disease or uncontrolled hypertension;
• Current diagnosis of anaemia or iron deficiency;
• Body weight instability (change in body weight of more than 5% over the preceding 3 months);
• Use of current regular prescription or over-the-counter medications that in the opinion of the Investigators may affect participant safety or outcome measures;
• Clinically significant abnormalities in screening blood tests abnormalities which in the opinion of the study physician, is clinically significant e.g. diabetes mellitus, hypothyroidism, renal impairment, abnormal liver function tests [bilirubin, alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT)] >3x upper limit of normal, other than due to fatty liver disease; Current pregnancy or breast-feeding in female volunteers (the Investigators will recommend using contraception for the duration of the visits to avoid participant drop-out);
• Pulse rate \<40 or >100 beats per minute OR systolic blood pressure >160 and \<100 OR diastolic blood pressure >95 and \<50 in the semi-supine position;
• Volunteer has participated in a clinical trial and has received an investigational product within the following time period prior to the first experimental visit in the current study: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer);
• Exposure to more than 3 new investigational medicinal products within 12 months prior to the scan;
• Vegan, gluten or lactose-intolerant (as test meals in the paradigms may include animal products, dairy and wheat products);
• Volunteers who have donated, or intend to donate, blood within three months before the screening visit or following study visit completion;
• Known history of SARS-CoV-2 infection (Covid-19) in the last 4 weeks;
• Ongoing symptoms suggestive of complications from previous SARS-CoV-2 infection ('long Covid-19') such as loss or change in sense of smell or taste, shortness of breath, palpitations, lethargy;
• SCOFF questionnaire score >1/5 indicating eating disorders (Luck et al. 2002);
• DSM-V criteria for alcohol use disorder (AUD) >2/11 indicating mild AUD (American-Psychiatric-Association 2013);
• Participants who have had previous obesity surgery or are on medications for obesity;
• Dutch Eating Behaviour Questionnaire (DEBQ) restraint score >3/5 indicating highly restrained eating behaviour.