Walker Jeanne M, Eckardt Patricia, Aleman Jose O, da Rosa Joel Correa, Liang Yupu, Iizumi Tadasu, Etheve Stephane, Blaser Martin J, L Breslow Jan, Holt Peter R
The Rockefeller University Hospital, New York.
Laboratory of Biochemical Genetics and Metabolism, Rockefeller University, New York.
J Clin Transl Res. 2018 Dec 7;4(2):122-135. eCollection 2019 Jan 10.
The metabolic syndrome (MetS) is a pathological condition comprised of abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. It has become a major threat globally, resulting in rapidly increasing rates of diabetes, coronary heart disease, and stroke. The polyphenol resveratrol (RES) is believed to improve glucose homeostasis and insulin resistance by activating sirtuin, which acetylates and coactivates downstream targets and affects glucose and lipid homeostasis in the liver, insulin secretion in the pancreas, and glucose uptake in skeletal muscle. We studied the effects of RES on insulin resistance, glucose homeostasis, and concomitant effects on adipose tissue metabolism and fecal microbiota in insulin-resistant subjects with the MetS.
A total of 28 obese men with the MetS were studied during a 35-day stay in the Rockefeller University Hospital metabolic unit. Subjects were randomized to receive RES 1 g orally twice daily or placebo while kept weight stable and consuming a western-style diet. At baseline, and after 30 days of RES or placebo administration, subjects underwent testing that included a euglycemic, hyperinsulinemic clamp, 2-h oral glucose tolerance test (GTT), resting energy expenditure, daily blood pressure monitoring, abdominal adipose tissue biopsy, and fecal and blood collections.
RES induced no changes in insulin resistance but reduced the 120-min time point and the area under the curve for glucose concentration in the 2-h GTT. In analysis, Caucasian subjects showed a significant improvement in insulin sensitivity and glucose homeostasis after GTT, whereas non-Caucasians showed no similar effects. Levels of fasting plasma RES and its primary metabolite dihydroresveratrol were variable and did not explain the racial differences in glucose homeostasis. RES administration to Caucasian subjects leads to an increase in several taxa including .
RES 2 g administered orally to obese men with MetS and insulin resistance marginally altered glucose homeostasis. However, in a small group of Caucasians, insulin resistance and glucose homeostasis improved. No concomitant changes in adipose tissue metabolism occurred, but fecal microbiota showed RES-induced changes.
The MetS increases the risk of diabetes, heart disease, and stroke. A major component of the syndrome is insulin resistance, resulting in systemic inflammation and hyperinsulinemia. The primary treatment consists of lifestyle changes, improved diet, and increased physical activity. This is often unsuccessful. In this study, RES was well tolerated. In Caucasian men, it significantly improved insulin sensitivity and glucose homeostasis. Similar results were found in studies that consisted exclusively of Caucasian men. However, RES presents a novel addition to the current treatment of the MetS and its sequelae.
代谢综合征（MetS）是一种由腹型肥胖、胰岛素抵抗、高血压和高脂血症组成的病理状态。它已成为全球的主要威胁，导致糖尿病、冠心病和中风的发病率迅速上升。多酚白藜芦醇（RES）被认为可通过激活沉默调节蛋白来改善葡萄糖稳态和胰岛素抵抗，该蛋白可使下游靶点乙酰化并共激活，影响肝脏中的葡萄糖和脂质稳态、胰腺中的胰岛素分泌以及骨骼肌中的葡萄糖摄取。我们研究了RES对患有MetS的胰岛素抵抗受试者的胰岛素抵抗、葡萄糖稳态以及对脂肪组织代谢和粪便微生物群的伴随影响。
共有28名患有MetS的肥胖男性在洛克菲勒大学医院代谢科住院35天期间接受研究。受试者被随机分为两组，一组每天口服两次1g RES，另一组服用安慰剂，同时保持体重稳定并食用西式饮食。在基线时以及RES或安慰剂给药30天后，受试者接受了多项测试，包括正常血糖、高胰岛素钳夹试验、2小时口服葡萄糖耐量试验（GTT）、静息能量消耗、每日血压监测、腹部脂肪组织活检以及粪便和血液采集。
RES未引起胰岛素抵抗的变化，但降低了2小时GTT中葡萄糖浓度的120分钟时间点及曲线下面积。在分析中，白人受试者在GTT后胰岛素敏感性和葡萄糖稳态有显著改善，而非白人受试者未表现出类似效果。空腹血浆RES及其主要代谢产物二氢白藜芦醇的水平各不相同，无法解释葡萄糖稳态的种族差异。对白人受试者给予RES导致包括……在内的几个分类群增加。
对患有MetS和胰岛素抵抗的肥胖男性口服2g RES对葡萄糖稳态的改变微乎其微。然而，在一小部分白人中，胰岛素抵抗和葡萄糖稳态得到改善。脂肪组织代谢未发生伴随变化，但粪便微生物群显示出RES诱导的变化。
MetS增加了患糖尿病、心脏病和中风的风险。该综合征的一个主要成分是胰岛素抵抗，导致全身炎症和高胰岛素血症。主要治疗方法包括生活方式改变、改善饮食和增加体育活动。但这通常并不成功。在本研究中，RES耐受性良好。在白人男性中，它显著改善了胰岛素敏感性和葡萄糖稳态。在仅由白人男性组成的研究中也发现了类似结果。然而，RES为目前MetS及其后遗症的治疗提供了一种新的补充。
