Polyphenols and Overfeeding (Poly-Nut)

Obesity is a complex and multifactorial disease representing a major public health challenge. Indeed, overweight and obese people carry a major risk of developing insulin resistance and type 2 diabetes mellitus. It has been demonstrated that polyphenols could be used to counteract some of the mechanisms involved in the generation of insulin resistance. The model of overfeeding represents a very good study model of the metabolic complications of obesity, since it has been shown to induce a transient state of insulin resistance in the human. The purpose of this research is to study the effects of a overfeeding (+50% of daily caloric needs over 31 days) with or without polyphenols supplementation (2g/days over 31 days) on insulin sensitivity measured in the setting of a hyperinsulinemic euglycemic clamp and on post prandial partitioning of exogenous lipids after a test meal. During 31 days, the volunteers will consume chocolate bars, chips, chocolate breads and cola in addition to their usual diet and will be supplemented with 2g of grape polyphenols extract or with placebo.

Overfeeding, Fat distribution, Subcutaneous and visceral adipose tissue, Insulin sensitivity, Insulin resistance, Peripheral and hepatic insulin sensitivity, Stable isotopes, Lipid oxidation, Energy expenditure, Muscle and subcutaneous adipose tissue gene expression

Volunteers will have peripheral and hepatic insulin sensitivity determined by using a two-stage hyperinsulinemic euglycemic clamp with stable isotopically labeled tracer infusion.

Endogenous glucose production (EGP) will be determined during the last 30 minutes of the low-dose insulin infusion.

Weight, height, waist and hip circumferences, fat mass using dual x-ray absorptiometry (DEXA) and abdominal fat distribution using resonance magnetic imaging (RMI).

13C enrichment will be measured in blood samples and breath test during a test meal performed before and after the 31 days of overfeeding.

Inclusion Criteria: Male Aged from 18 to 55 years Body Mass Index of 23 to 27 kg/m² Normal blood pressure Fasting glycemia < 7 mmol/L CRPus < 10mg/L Triglycerides ≤ 3mmol/L Exclusion Criteria: Medical or surgical history which may affect the results (renal -cardiovascular - hepatic- endocrine-inflammatory diseases) Subjects under treatment which may interfere with the measured parameters Eating disorder Intensive sportive activity Dairy products allergy or intolerance

Bartova S, Madrid-Gambin F, Fernandez L, Carayol J, Meugnier E, Segrestin B, Delage P, Vionnet N, Boizot A, Laville M, Vidal H, Marco S, Hager J, Moco S. Grape polyphenols decrease circulating branched chain amino acids in overfed adults. Front Nutr. 2022 Oct 26;9:998044. doi: 10.3389/fnut.2022.998044. eCollection 2022.

Segrestin B, Delage P, Nemeth A, Seyssel K, Disse E, Nazare JA, Lambert-Porcheron S, Meiller L, Sauvinet V, Chanon S, Simon C, Ratiney H, Beuf O, Pralong F, Yassin NA, Boizot A, Gachet M, Burton-Pimentel KJ, Vidal H, Meugnier E, Vionnet N, Laville M. Polyphenol Supplementation Did Not Affect Insulin Sensitivity and Fat Deposition During One-Month Overfeeding in Randomized Placebo-Controlled Trials in Men and in Women. Front Nutr. 2022 May 9;9:854255. doi: 10.3389/fnut.2022.854255. eCollection 2022.