Study of the Mechanisms of Metabolic Adaptations to Overfeeding

Not Applicable

• Conditions: Diabetes; Obesity
• Interventions: Other: Hypercaloric diet; Dietary Supplement: placebo (for polyphenols); Dietary Supplement: polyphenols

• Registration Number: NCT02225457
• Lead Sponsor: Centre Hospitalier Universitaire Vaudois

Brief Summary

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

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.

Study Timeline

• Study Start: 2013-12
• Study First Submitted: 2014-07-21
• Study First Submitted QC: 2014-08-25
• Study First Posted: 2014-08-26
• Status Verified: 2016-03
• Last Update Submitted: 2016-03-05
• Last Update Posted: 2016-03-08
• Primary Completion: 2016-05
• Study Completion: 2017-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

• normal healthy male and female volunteer

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Hypercaloric diet and placebo	placebo (for polyphenols)	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.
Hypercaloric diet and polyphenols	Hypercaloric diet	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.
Hypercaloric diet and polyphenols	polyphenols	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.
Hypercaloric diet and placebo	Hypercaloric diet	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.

Primary Outcome Measures

Name	Time	Method
Change from baseline in insulin sensitivity	baseline, day 31 of overfeeding	Whole body insulin sensitivity will be measured during hyperinsulinemic, euglycemic clamps.

Secondary Outcome Measures

Name	Time	Method
Change from baseline in muscle and adipose tissue gene expression	Baseline, day 28 of overfeeding	Transcriptomic experiments will be performed on muscle and adipose tissue samples

Trial Locations

Locations (1)

CHUVaudois; 🇨🇭 Lausanne, Vaud, Switzerland