# Precision nutrition in weight loss and neuroendocrine control of people with obesity: The study protocol of a factorial randomised controlled trial (GenON Programme)

## TL;DR

This study tests if personalized nutrition based on genetic risk improves weight loss and health outcomes in people with obesity.

## Contribution

The study introduces a factorial trial design combining genetic risk assessment with tailored dietary interventions for obesity.

## Key findings

- Participants receiving satiety-focused counseling may experience improved weight loss and satiety control.
- Genetic risk profiling could influence metabolic and neuroendocrine outcomes in overweight individuals.
- The trial will assess the impact of high-protein breakfasts and behavioral strategies on body composition and cardiometabolic markers.

## Abstract

Precision nutrition, guided by genetic testing, has emerged as a promising approach for managing obesity. However, robust clinical trials testing its effectiveness in real‐world dietary interventions remain scarce. The GenOn Programme aims to evaluate whether tailoring nutritional care based on genetic risk for obesity enhances weight loss, satiety control, and metabolic outcomes in adults with overweight and obesity.

The GenOn Programme is an 18‐week, 2 × 2 factorial, randomised controlled trial including 120 adults classified as high or low genetic risk for obesity (variants: FTO rs9939609 and rs1121980; MC4R rs1782313; LEP rs7799039). Participants are randomised to standard or satiety‐focused dietary counselling. Both groups receive five calorie‐restricted (−500 kcal/day), nutritionally balanced meal plans. The satiety arm additionally includes a high‐protein breakfast, daily granola supplementation and behavioural strategies. Assessments at baseline, Week 12, and Week 18 include weight loss, body composition, satiety perception, quality of life, cardiometabolic markers, (epi)genetics, inflammation, neuroendocrine regulation, and metagenomics.

The GenOn Programme is a randomised controlled trial to test a precision nutrition approach for overweight and obesity, integrating genetics, dietary strategies, and behavioural support. Findings may inform dietitians and healthcare systems on the clinical value of genetically guided nutritional care to improve outcomes in the treatment of overweight and obesity.