Study of the Mechanisms of Metabolic Adaptations to Overfeeding

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

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.

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.

Inclusion Criteria:

• normal healthy male and female volunteer

Exclusion Criteria:

• Diabetes mellitus
• High blood pressure
• Liver disease
• Kidney disease