The goal of this randomized trial is to: 1) investigate the immunological landscape of patients with obesity and conduct an in-depth functional characterization of their immune system; and 2) precisely define the effects of time-restricted feeding (TRF) on immune function in patients with obesity; 3) uncover the underlying mechanisms by which TRF modulates the immune system patients with obesity through a multi-omics approach.

The main questions it aims to answer are: i) what is the underlying cause of impaired immunocompetence in patients with obesity? ii) how nutritional interventions improve the immune function of patients with obesity? Patients with obesity following TRF (8 h eating window ranging from 6-8 am to 14-16 pm) will be compared to patients with obesity without TRF control schedule (14h eating window ranging from 6-8 am to 8-10 pm). In addition to patients with obesity, the present study aims to recruit a group of a reference healthy group (BMI between 18.5-24.9 kg/m²) that will not receive any nutritional intervention.

The following endpoints will be collected: Body weight and composition using Bioelectrical Impedance Analysis, resting energy expenditure (REE) using indirect calorimetry, blood glucose levels using a continuous glucose monitoring (CGM) device, metabolic parameters (fasting blood glucose levels, C-peptide, HbA1c, insulin, HOMA-IR, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, hepatic enzymes), and cytokine profile.

Blood and stool, samples will be collected to establish metagenomic, transcriptomic, cytomic and metabolomic analyses.

Inclusion Criteria:

Patients with obesity

• Women
• Age 18-64 years
• Body mass Index between 40-50 kg/m²
• Self-reported eating pattern window of more than 14h
• Three meal eating pattern
• Stable body weight (less than 10% of current body weight during the last 3 months)
• Social security affiliation
• Written consent
• Good understanding of the French language

Lean patients

• Women
• Age 18-64 years
• Body mass Index between 18.5-24.9 kg/m²
• Self-reported eating pattern window of more than 14h
• Social security affiliation
• Written consent
• Good understanding of the French language

Exclusion Criteria:

• Diabetes type I or II
• Major cardiovascular disease
• Pregnancy
• Medication that could affect the study outcomes (i.e. anti-inflammatory drugs, antibiotics, immunosuppressors)
• Use products intended for weight loss
• Night work shift
• Past record of malignant tumors
• Serious liver dysfunction or chronic kidney disease
• Eating disorders
• Chronic viral disease (Hepatitis B or C, HIV) or inflammatory systemic diseases (i.e. Crohn's disease, rheumatoid arthritis)
• Serious cardiovascular or cerebrovascular disease within 6 months before randomization
• Severe gastrointestinal diseases or gastrointestinal surgery in the 12 months before randomization
• Under guardianship, curatorship, deprived of liberty
• Unable or unwilling to sign the informed consent form.
• Patient on AME (state medical aid)

Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared

Two years after the last publication

Data sharing must be accepted by the sponsor and the PI based on a scientific project and scientific involvement of the PI team. Collaboration will be fostered. The founder could be involved in the decision. Teams wishing obtain IPD must meet the sponsor and IP team to present scientifics (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractualization. Processing of shared data must comply with European General Data Protection Regulation (GDPR).