Investigating the Effects of 24 Hour LEAP2 Infusion in Individuals With Overweight and Obesity

This study investigates whether temporarily blocking the ghrelin receptor affects appetite and food intake in people with overweight or obesity. Ghrelin is a hormone that stimulates hunger; the researchers are using LEAP2, a naturally occurring hormone that blocks ghrelin's receptor, as a research tool to study what happens when ghrelin signaling is turned off for 24 hours. The study is a randomized, double-blind, placebo-controlled crossover trial. Eighteen adults with overweight or obesity (BMI ≥25 kg/m², elevated body fat percentage) will each complete two 24-hour study visits, at least 7 days apart: one with a continuous LEAP2 infusion and one with a saline placebo infusion, in random order. Neither participants nor most study staff will know which treatment is given on which visit. During each 24-hour visit, participants will receive a standardized liquid test meal followed by ad libitum (eat-until-comfortably-full) lunch, dinner, and breakfast meals, plus access to snacks. The main question the study aims to answer is whether LEAP2 reduces the total amount of food eaten over 24 hours compared to placebo. Additional measurements include blood glucose levels, subjective feelings of hunger and fullness (via questionnaires), stomach emptying rate, blood pressure and heart rate, and hormone levels (including growth hormone, FSH, and LH). Some participants will also undergo a small fat tissue biopsy to study how genes and proteins related to metabolism respond. The results are expected to improve understanding of how ghrelin and LEAP2 regulate appetite and metabolism in people with obesity, which may inform future approaches to treating obesity and related metabolic conditions.

Inclusion Criteria: * Age between 18 and 65 years old * Body mass index (BMI) ≥ 25 kg/m2 * Body fat mass ≥ 20% for male individuals and ≥ 30% for female individuals * Informed oral and written consent Exclusion Criteria: * Anemia * Plasma alanine aminotransferase (ALT) \> 2 times normal value * History of hepatobiliary and/or gastrointestinal disorder * eGFR \< 60 * Regular tobacco smoking and/or use of other nicotine products * Type 1 or type 2 diabetes medical treatment * Women of childbearing potential who are not using effective contraception * Pregnancy or breastfeeding * Any ongoing medication or medical condition that investigators evaluate would interfere with study participation.