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

Summary

The goal of this interventional study is to measure the blood levels of the gut hormones LEAP2 and acyl ghrelin (AG), appetite and food intake after consuming liquid meals of different caloric sizes, in healthy adults with and without obesity.

AG is a stomach-derived homone that increases appetite, and LEAP2 a liver-gut derived hormone that decreases appetite, which interferes the action of AG ant its receptor in the brain called the growth hormone secretagogue receptor (GHSR). Blood levels of AG and LEAP2 change in opposite directions after food intake (AG decreasing, LEAP2 increasing). AG is formed from an inactive version of hormone called desacyl ghrelin (DAG). Previous studies have shown that greater food intake leads to a greater decrease in blood levels of total ghrelin (AG + DAG), but this has not been studied for changes in blood AG or LEAP2 after eating. Blood levels of AG and total ghrelin when fasted and after food intake are lower, while blood levels of LEAP2 are higher, in adults with than those without obesity.

The main study questions are:

1. Are there greater increases in blood levels of LEAP2 and greater decreases in blood levels of AG after consuming larger meals (by amount of calories they contain)?
2. Are greater decreases in appetite after connsuming larger meals related to greater increases in blood levels of LEAP2 and greater decreases in blood levels of AG?
3. Are greater decreases in food intake at a buffet lunch after consuming larger meals eaten a few hours previously related to greater increases in blood levels of LEAP2 and greater decreases in blood levels of AG?
4. Do the above findings differ between adults without obesity and with obesity?

At each of 4 study days, healthy adults (without and with obesity) will consume one size of a single liquid meal containing different amounts of calories (0, 600, 900 (group without obesity only), 1200, 1800 (group with obesity only) kilocalories, of identical total volume) after an overnight fast and have measurements of blood LEAP2 and AG and appetite ratings from 0 to 180 min, and have food intake at an ad libitum lunch measured at 180 mins. Food will be weighed and converted into kilocalories.

All participants will attend for all 4 study visits in a randomised order to receive one of the meal sizes at each visit, so that all 4 meal zizes are consumed over all 4 study visits: 0, 600, 900 (group without obesity), 1200, 1800 (group with obesity) kcal.

Conditions

• Eating Behavior
• Obesity
• Appetitive Behavior

Interventions

DIETARY_SUPPLEMENT

0 kcal liquid meal

Flavoured water, given as one meal at one study visit only

DIETARY_SUPPLEMENT

600 kcal liquid meal

Fortisip Compact Vanilla, given as one meal at one study visit only

DIETARY_SUPPLEMENT

900 kcal liquid meal (only for group without obesity)

Fortisip Compact Vanilla, given as one meal at one study visit only

DIETARY_SUPPLEMENT

1200 kcal liquid meal

Fortisip Compact Vanilla, given as one meal at one study visit only

DIETARY_SUPPLEMENT

1800 kcal liquid meal (only for group with obesity)

Fortisip Compact Vanilla, given as one meal at one study visit only

Sponsors & Collaborators

• Imperial College London

  lead OTHER

Principal Investigators

• Tony Goldstone, MRCP PhD · Imperial College London

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2023-08-29

Primary Completion

2025-08-31

Completion

2025-08-31

Countries

• United Kingdom

Study Locations