Study of the Mechanisms of Metabolic Adaptations to Overfeeding

Study Overview
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Brief Summary
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Obesity results from complex interactions between genetic and environmental factors, and are strongly associated with metabolic complications such as type 2 diabetes mellitus. Obesity is defined as an excessive fat accumulation that presents a risk to health, a risk that is highly dependent upon the type of adipose tissue accumulation, whether visceral or sub-cutaneous, but also upon the characteristics of the fat tissue, especially inflammatory cells accumulation. Because of the well known sexual difference in fat accretion, this obesity-associated risk may also be very different for men and for women. In addition, recent data indicate that various factors such as the intestinal microbiota, but also the dietary intake of protective nutrients might be important determinants of the metabolic complications of obesity. Here we propose to: 1) study the metabolic adaptations and the mechanisms of adipose tissue accumulation during a period of controlled caloric over-nutrition, both in men and in women; 2) evaluate the potential protective effects of a supplementation with polyphenols on insulin resistance and other metabolic adaptations.

Detailed Description
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To achieve these goals, healthy male and female volunteers will be enrolled into a one month longitudinal, prospective study on the influence of hypercaloric overfeeding (+50% of daily caloric needs) on different tissues (adipose tissue, muscle and blood). They will be separated into two different groups: hypercaloric nutrition and placebo, and hypercaloric nutrition and polyphenols (2g/day), where polyphenols administration will be randomized and administered in a double blind fashion. Whole body and hepatic insulin sensitivity, total energy expenditure, glucose hepatic production, protein and gene expression in muscle, adipose tissue and blood as well as intestinal microbiota will be assessed at base line, and after one month of overfeeding.

Official Title
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Study of the Determinants and Mechanisms of Adaptation of Metabolic Responses to Controlled Overfeeding in Female and Male Healthy Volunteers

Conditions
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Obesity, Diabetes

Intervention / Treatment
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* Other: Hypercaloric diet
* Dietary Supplement: polyphenols
* Dietary Supplement: placebo (for polyphenols)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: normal healthy male and female volunteer Exclusion Criteria: Diabetes mellitus High blood pressure Liver disease Kidney disease

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypercaloric diet and polyphenols<br>polyphenols will consist in the administration of 1 gram (5x200 mg) of the compound bid during the entire overfeeding period. Hypercaloric diet will consist in a hypercaloric diet providing an excess of 50% KCal over daily requirements, and will last 30 days. | Other: Hypercaloric diet<br>* Hypercaloric diet will be designed to provide 50% excess in calories compared to daily requirements. It will consist in a snack type, high fat and high carbohydrates diet.<br>* Other names: Overfeeding;Dietary Supplement: polyphenols<br>* Administration of polyphenols will consist in the administration of 1 gram (5x200 mg) of the compound bid during the entire overfeeding period.<br>|
| Active Comparator: Hypercaloric diet and placebo<br>Placebo will consist in the administration of a number of placebo pills matching that of polyphenols, in a similar way (bid) for the duration of the overfeeding experiment. Overfeeding will consist in a hypercaloric diet providing an excess of 50% KCal over daily requirements, and will last 30 days. | Other: Hypercaloric diet<br>* Hypercaloric diet will be designed to provide 50% excess in calories compared to daily requirements. It will consist in a snack type, high fat and high carbohydrates diet.<br>* Other names: Overfeeding;Dietary Supplement: placebo (for polyphenols)<br>* Placebo will consist in the administration of a number of placebo pills matching that of polyphenols, in a similar way (bid) for the duration of the overfeeding experiment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in insulin sensitivity | Whole body insulin sensitivity will be measured during hyperinsulinemic, euglycemic clamps. | baseline, day 31 of overfeeding | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in muscle and adipose tissue gene expression | Transcriptomic experiments will be performed on muscle and adipose tissue samples | Baseline, day 28 of overfeeding | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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polyphenols, insulin resistance, type 2 diabetes, obesity, adipose tissue, overfeeding