Healthy vs Unhealthy Obesity: Mehanistic Insights and Effects of Time-Restricted Eating

Study Overview
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Brief Summary
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Obesity-related cardiometabolic diseases are now a leading cause of death worldwide. These diseases result from a dysfunctional adipose tissue (AT) that induces inflammation, insulin resistance and altered endocrine function. However, not all obese people develop metabolic complications, which has given rise to the concept of metabolically healthy obesity (MHO). Recent evidence suggests that intermittent fasting methods, in particular time-restricted eating (TRE) may be effective in improving cardiometabolic health, independently of weight loss, and this could be particularly effective in MUO subjects. The investigators hypothesize that in young male adults TRE is a more effective/beneficial approach in MUO than in MHO due to the weight loss-independent improvement in their inflammatory and metabolic derangements. To this aim, a 16-week 8h TRE intervention study will be performed in MHO and MUO subjects, assessing anthropometric, endocrine, and other outcomes.

Detailed Description
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Although clinical differences between metabolically healthy and unhealthy obesity (MHO and MUO, respectively) have been extensively described, cellular mechanisms involved in these different phenotypes are largely unknown. This evidence is crucial for proposing preventive and therapeutic approaches. Recently, intermittent fasting methods, in particular time-restricted eating (TRE, a self-selected daily limited eating window protocol), have shown to be effective in improving cardiometabolic health, independently of weight loss, which could be particularly relevant in MUO. The investigators will recruit young (20-22y-old) males with obesity (Body Mass Index≥30) and classify them as MHO or MUO (≤1 or ≥3 metabolic syndrome risk factors, respectively). A 16-week, 8h TRE intervention will be conducted in MHO vs. MUO subgroups, to assess and compare the anthropometric, metabolic, endocrine, inflammatory and peripheral blood mononuclear cell (PBMC) mechanistic/signaling response. The investigators expect to advance the understanding of cellular mechanisms implicated in MHO and MUO, including potential therapeutic targets. Ultimately, the investigators expect to find relevant opportunities for intervention to prevent the serious cardiometabolic consequences of obesity.

Official Title
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Healthy vs Unhealthy Obesity in Young Male Adults: Early Predictors, Mechanistic Insights and Effects of Time-Restricted Eating

Conditions
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Metabolically Healthy Obesity, Intermittent Fasting

Intervention / Treatment
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* Behavioral: Time-restricted eating


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Belong to the GOCS cohort at INTA BMI≥30 Own and use a Smartphone with Apple iOS or Android OS Baseline eating period ≥ 13 h per day. Exclusion Criteria: Medications for any metabolic syndrome disorder Shift workers Known inflammatory and/or rheumatologic disease History of cardiovascular event Thyroid or adrenal disease, malignancy or diabetes History of eating disorder. Special diet (e.g., celiac disease),or any other disease or treatment that may interfere with the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: TRE intervention comparing MHO vs MUO
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MHO<br>metabolically healthy obese subjects undergoing TRE | Behavioral: Time-restricted eating<br>* 16 weeks of TRE consisting of an 8-hour eating window.<br>* Other names: Intermittent fasting;|
| Experimental: MUO<br>metabolically unhealthy obese subjects undergoing TRE | Behavioral: Time-restricted eating<br>* 16 weeks of TRE consisting of an 8-hour eating window.<br>* Other names: Intermittent fasting;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TG | Fasting triglycerides | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Waist circumference |  | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Time restricted eating, Metabolic health, PBMC, Adipokines