University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, Australia; Department of Nutrition and Dietetics, Princess Alexandra Hospital, Brisbane, Australia.
School of Medicine Metro-South, University of Queensland, Brisbane, Australia; Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia.
Clin Gastroenterol Hepatol. 2014 Dec;12(12):2092-103.e1-6. doi: 10.1016/j.cgh.2014.02.024. Epub 2014 Feb 25.
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD), characterized by accumulation of hepatic triglycerides (steatosis), is associated with abdominal obesity, insulin resistance, and inflammation. Although weight loss via calorie restriction reduces features of NAFLD, there is no pharmacologic therapy. Resveratrol is a polyphenol that prevents high-energy diet-induced steatosis and insulin resistance in animals by up-regulating pathways that regulate energy metabolism. We performed a placebo-controlled trial to assess the effects of resveratrol in patients with NAFLD.
Overweight or obese men diagnosed with NAFLD were recruited from hepatology outpatient clinics in Brisbane, Australia from 2011 through 2012. They were randomly assigned to groups given 3000 mg resveratrol (n = 10) or placebo (n = 10) daily for 8 weeks. Outcomes included insulin resistance (assessed by the euglycemic-hyperinsulinemic clamp), hepatic steatosis, and abdominal fat distribution (assessed by magnetic resonance spectroscopy and imaging). Plasma markers of inflammation, as well as metabolic, hepatic, and antioxidant function, were measured; transcription of target genes was measured in peripheral blood mononuclear cells. Resveratrol pharmacokinetics and safety were assessed.
Eight-week administration of resveratrol did not reduce insulin resistance, steatosis, or abdominal fat distribution when compared with baseline. No change was observed in plasma lipids or antioxidant activity. Levels of alanine and aspartate aminotransferases increased significantly among patients in the resveratrol group until week 6 when compared with the placebo group. Resveratrol did not significantly alter transcription of NQO1, PTP1B, IL6, or HO1 in peripheral blood mononuclear cells. Resveratrol was well-tolerated.
Eight weeks administration of resveratrol did not significantly improve any features of NAFLD, compared with placebo, but it increased hepatic stress, based on observed increases in levels of liver enzymes. Further studies are needed to determine whether agents that are purported to mimic calorie restriction, such as resveratrol, are safe and effective for complications of obesity. Clinical trials registration no: ACTRN12612001135808.
非酒精性脂肪性肝病（NAFLD）的特征是肝内三酰甘油（脂肪变性）积聚，与腹部肥胖、胰岛素抵抗和炎症有关。虽然通过热量限制减轻体重可减少 NAFLD 的特征，但尚无药物治疗。白藜芦醇是一种多酚，可通过上调调节能量代谢的途径，预防高能饮食诱导的动物脂肪变性和胰岛素抵抗。我们进行了一项安慰剂对照试验，以评估白藜芦醇在 NAFLD 患者中的作用。
2011 年至 2012 年，从澳大利亚布里斯班的肝脏门诊诊所招募了超重或肥胖且被诊断为 NAFLD 的男性。他们被随机分为两组，每天分别给予 3000 毫克白藜芦醇（n = 10）或安慰剂（n = 10）治疗 8 周。结果包括胰岛素抵抗（通过正葡萄糖高胰岛素钳夹评估）、肝脂肪变性和腹部脂肪分布（通过磁共振波谱和成像评估）。测量了炎症、代谢、肝脏和抗氧化功能的血浆标志物；测量了外周血单核细胞中靶基因的转录。评估了白藜芦醇的药代动力学和安全性。
与基线相比，8 周的白藜芦醇治疗并未降低胰岛素抵抗、脂肪变性或腹部脂肪分布。血浆脂质或抗氧化活性没有变化。与安慰剂组相比，白藜芦醇组的患者在第 6 周时丙氨酸和天冬氨酸转氨酶水平显著升高。白藜芦醇在外周血单核细胞中对 NQO1、PTP1B、IL6 或 HO1 的转录没有显著改变。白藜芦醇耐受性良好。
与安慰剂相比，8 周的白藜芦醇治疗并未显著改善 NAFLD 的任何特征，但根据观察到的肝酶水平升高，它增加了肝脏应激。需要进一步的研究来确定是否像白藜芦醇这样据称模拟热量限制的药物对肥胖相关并发症是安全有效的。临床试验注册号：ACTRN12612001135808。
Zotero 插件