Polyphenol Supplementation Did Not Affect Insulin Sensitivity and Fat Deposition During One-Month Overfeeding in Randomized Placebo-Controlled Trials in Men and in Women

Bérénice Segrestin, Pauline Delage, Angéline Nemeth, Kevin Seyssel, Emmanuel Disse, Julie-Anne Nazare, Stéphanie Lambert-Porcheron, Laure Meiller, Valerie Sauvinet, Stéphanie Chanon, Chantal Simon, Hélène Ratiney, Olivier Beuf, François Pralong, Naba-Al-Huda Yassin, Alexia Boizot, Mélanie Gachet, Kathryn J Burton-Pimentel, Hubert Vidal, Emmanuelle Meugnier, Nathalie Vionnet, Martine Laville, Bérénice Segrestin, Pauline Delage, Angéline Nemeth, Kevin Seyssel, Emmanuel Disse, Julie-Anne Nazare, Stéphanie Lambert-Porcheron, Laure Meiller, Valerie Sauvinet, Stéphanie Chanon, Chantal Simon, Hélène Ratiney, Olivier Beuf, François Pralong, Naba-Al-Huda Yassin, Alexia Boizot, Mélanie Gachet, Kathryn J Burton-Pimentel, Hubert Vidal, Emmanuelle Meugnier, Nathalie Vionnet, Martine Laville

Abstract

Two randomized placebo-controlled double-blind paralleled trials (42 men in Lyon, 19 women in Lausanne) were designed to test 2 g/day of a grape polyphenol extract during 31 days of high calorie-high fructose overfeeding. Hyperinsulinemic-euglycemic clamps and test meals with [1,1,1-13C3]-triolein were performed before and at the end of the intervention. Changes in body composition were assessed by dual-energy X-ray absorptiometry (DEXA). Fat volumes of the abdominal region and liver fat content were determined in men only, using 3D-magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) at 3T. Adipocyte's size was measured in subcutaneous fat biopsies. Bodyweight and fat mass increased during overfeeding, in men and in women. While whole body insulin sensitivity did not change, homeostasis model assessment of insulin resistance (HOMA-IR) and the hepatic insulin resistance index (HIR) increased during overfeeding. Liver fat increased in men. However, grape polyphenol supplementation did not modify the metabolic and anthropometric parameters or counteract the changes during overfeeding, neither in men nor in women. Polyphenol intake was associated with a reduction in adipocyte size in women femoral fat. Grape polyphenol supplementation did not counteract the moderated metabolic alterations induced by one month of high calorie-high fructose overfeeding in men and women. The clinical trials are registered under the numbers NCT02145780 and NCT02225457 at ClinicalTrials.gov and available at https://ichgcp.net/clinical-trials-registry/NCT02145780 and https://ichgcp.net/clinical-trials-registry/NCT02225457.

Keywords: gender difference; grape polyphenols; insulin resistance; insulin sensitivity; nutritional intervention; overfeeding; polyphenols.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Segrestin, Delage, Nemeth, Seyssel, Disse, Nazare, Lambert-Porcheron, Meiller, Sauvinet, Chanon, Simon, Ratiney, Beuf, Pralong, Yassin, Boizot, Gachet, Burton-Pimentel, Vidal, Meugnier, Vionnet and Laville.

Figures

FIGURE 1
FIGURE 1
Flow chart of the study. (A) Men. (B) Women.
FIGURE 2
FIGURE 2
Evolution of glycemia, insulinemia, triglycerides and 13C-C18:1 triglycerides in plasma during the test meal, in men and women in the placebo and the polyphenol groups. MISI: Matsuda insulin sensitivity index, iAUC in each group are represented before and after overfeeding. White squares: Placebo group at baseline; White circles: Placebo group after overfeeding; Black squares: Polyphenol group at baseline; Black circles: Polyphenol group after overfeeding; White bars: Baseline; Hatched bars: Overfeeding. Data are expressed as mean ± SEM.
FIGURE 3
FIGURE 3
(A) Evolution of android and gynoid fat mass in both populations analyzed by DEXA. T-test or Wilcoxon, * p < 0.05. White bars: Placebo group; Black bars: Polyphenol group. Data are expressed as mean ± SEM. (B) Periumbilical adipocyte area in men (A) and women (B) and gluteal adipocyte area in women (D) before (D-7) and after overfeeding (D28) (μm2) in each group. Periombilical adipose tissue pictures of a subject in the placebo and polyphenol group at baseline and after overfeeding (C). ANOVA with repeated measures or non- parametric test when appropriate were performed to study the effect of time and the effect of the polyphenol supplementation. No effect of Time*Group using ANOVA repeated measures, or non-parametric test, except for the Gluteofemoral adipocyte size in women. White bars: Baseline; Hatched bars: Overfeeding. Data are expressed as mean ± SEM.

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