The effects of polyphenol supplementation on adipose tissue morphology and gene expression in overweight and obese humans

<p>Dietary polyphenols have beneficial effects on adipose tissue mass and function in rodents, but human studies are scarce. In a randomized, placebo-controlled study, 25 (10 women) overweight and obese humans received a combination of the polyphenols epigallocatechin-gallate and resveratrol (282 mg/d, 80 mg/d, respectively, EGCG+RES, n = 11) or placebo (PLA, n = 14) supplementation for 12 weeks. Abdominal subcutaneous adipose tissue (SAT) biopsies were collected for assessment of adipocyte morphology and micro-array analysis. EGCG+RES had no effects on adipocyte size and distribution compared with PLA. However, we identified pathways contributing to adipogenesis, cell cycle and apoptosis were significantly downregulated by EGCG+RES <i>versus</i> PLA. Furthermore, EGCG+RES significantly decreased expression of pathways related to energy metabolism, oxidative stress, inflammation, and immune defense as compared with PLA. In conclusion, the SAT gene expression profile indicates a reduced cell turnover after 12-week EGCG+RES in overweight-obese subjects. It remains to be elucidated whether these alterations translate into long-term metabolic effects.</p

Correlation between the change in adipocyte diameter and insulin sensitivity after 26-wks VAL or PLB treatment (<i>n</i> = 30)

<p>The decrease in adipocyte size was significantly associated with alterations in insulin sensitivity after VAL (n = 14, closed circles) and PLB (n = 16, open circles) treatment (<i>r</i> = −0.452, <i>P</i> = 0.012).</p

Fasting and postprandial ATBF

<p>VAL treatment (<i>n</i> = 16) significantly increased both (<b>A</b>) fasting ATBF and (<b>B</b>) postprandial ATBF (<i>P</i> = 0.049) compared with PLB (<i>n</i> = 14). A high-fat mixed-meal (containing 2.6 MJ, consisting of 61E% fat (35.5E% saturated fatty acids (FAs), 18.8E% monounsaturated FAs and 1.7E% polyunsaturated FAs), 33E% carbohydrate and 6E% protein) was ingested at t0 min. Values are means±SEM. *<i>P</i><0.05 VAL vs. PLB. ATBF, adipose tissue blood flow.</p

Enrollment flow chart.

<p>Enrollment flow chart.</p

Subject characteristics before and after 26-wks treatment with VAL or PLB.

<p>BMI, body mass index; HbA1C, glycated haemoglobin; NEFA, non-esterified fatty acid; SBP, systolic blood pressure; DBP, diastolic blood pressure; TAG, triacylglycerol; WHR, waist-to-hip ratio; <i>N.S.</i>, not significant. ^*VAL <i>vs.</i> PLB treatment assessed by repeated-measures ANOVA. ^#<i>P</i><0.05 <i>vs</i>. PLB. Values are means±SEM.</p

Abdominal subcutaneous AT gene expression before and after 26-wks treatment with VAL or PLB.

<p>PPARγ, peroxisome proliferator-activated receptor γ; aP2, adipocyte fatty acid binding protein; C/EBPα, CCAAT/enhancer binding protein α; VEGF, vascular endothelial growth factor; ANG, angiogenin; CTSS, cathepsin S; ATGL, adipose triglyceride lipase; CGI-58, comparative gene indentification 58; G0S2, G0/G1 switch gene 2; HSL, hormone-sensitive lipase. ^*VAL <i>vs.</i> PLB treatment assessed by repeated-measures ANOVA. Values are medians (interquartile range).</p

Circulating inflammatory markers

<p>VAL treatment (<i>n</i> = 17) did not significantly affect plasma concentrations of (<b>A</b>) MCP-1, (<b>B</b>) TNF-α, (<b>C</b>) adiponectin and (<b>D</b>) leptin compared with PLB (<i>n</i> = 19). MCP-1, monocyte chemoattractant protein-1; TNF-α, tumour necrosis factor-α.</p

Mean adipocyte diameter and adipocyte size distribution

<p>VAL treatment (<i>n</i> = 15) significantly reduced (<b>A</b>) adipocyte size compared with PLB (<i>n</i> = 16), with (<b>B</b>) a shift toward a higher proportion of small adipocytes. Values are means±SEM. *<i>P</i><0.05, ^#<i>P</i><0.01, ^†<i>P</i><0.001 VAL vs. PLB.</p