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Resveratrol Potentiates the Insulin Sensitizing Effects on Adipose Tissue of Overweight Human Subjects
Roger Maginley, Kehao Zhang, Akankasha Goyal, Oana A. Sandu, Preeti Kishore, Meredith Hawkins, Michelle Carey. Endocrinology, Albert Einstein College of Medicine, New York, New York, United States

Purpose of Study Importantly, this plant based polyphenol proved beneficial metabolic effects in rodent studies, including improved insulin sensitivity, reduced inflammation, and increased muscle mitochondrial biogenesis. Our studies would test these findings in insulin resistant, overweight human subjects by examining the effects of resveratrol on insulin sensitivity, muscle mitochondria and adipose tissue inflammation.
Methods Used We administered a dose of 2 gm/day Resveratrol RV or placebo PL for 28 days in a randomized, double-blinded study to n=21 non-diabetic subjects (17 M; Age=52±2; BMI=31.9±0.9 kg/m2; HOMA-IR=3.9±0.2). The subjects participated in 6-hour, stepped euglycemic hyperinsulinemic (30 and 80 mU/m2.min) ‘pancreatic clamp' studies to assess hepatic and peripheral insulin sensitivity. We then performed biopsy of vastus lateralis muscle and subcutaneous abdominal adipose tissue, before and after RV and PL. We analyzed muscle mitochondria wfor quantity, size, area in a field and the percent area covered, using electron microscopy with Volocity image analysis.
Summary of Results Resveratrol induced an increase of 22% (p=0.035) in glucose uptake, even if it did not affect glucose production. There were no changes in the basal energy expenditure (Kcal/day) and respiratory quotient, as assessed by indirect calorimetry (Parvo Medics). No effect in muscle strength in these healthy overweight middle-aged subjects was seen. There were no changes in quantity (p=0.829) or percent area (p=0.897) of muscle mitochondria. Notably, resveratrol reduced inflammation in adipose tissue, with decreased expression of the pro-inflammatory cytokines TNFα and IL6 in whole fat (by 68% and 52%, p<0.05), and of IL6 and PAI-1 in adipose macrophages (by 50% and 40%, p<0.05). Adiponectin expression in whole fat increased more than 50% in resveratrol treated subjects. Further, we observed increased expression of genes associated with ‘browning' of adipose tissue: UCP1 showed 46.6% increase and PGC-1α 34.9%.
Conclusions Resveratrol improves insulin sensitivity, even if not accompanied by changes in the size or number of muscle mitochondria; perhaps this anti-inflammatory and ‘browning' effects in adipose tissue could contribute to favorable metabolic effects in insulin resistant humans.


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