Resveratrol Does Not Benefit Patients With Nonalcoholic Fatty Liver Disease
Resveratrol Does Not Benefit Patients With Nonalcoholic Fatty Liver Disease
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DOI：
10.1016/j.cgh.2014.02.024
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发表时间：
2014-12-01
影响因子：
12.6
通讯作者：
Hickman, Ingrid J.
中科院分区：
文献类型：
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作者：
Chachay, Veronique S.;Macdonald, Graeme A.;Hickman, Ingrid J.
背景与目的：非酒精性脂肪性肝病（NAFLD），其特征是肝脏甘油三酯（脂肪变性）的积累，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以减少NAFLD的特征，但没有药物治疗。白藜芦醇是一种多酚，通过上调调节能量代谢的途径，防止高能量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，以评估白藜芦醇对NAFLD.METHODS患者的影响：从2011年到2012年，在澳大利亚布里斯班的肝病门诊招募了超重或肥胖的NAFLD男性。他们被随机分配到每天给予3000 mg白藜芦醇（n = 10）或安慰剂（n = 10）的组，持续8周。结果包括胰岛素抵抗（通过正常血糖-高胰岛素钳夹评估）、肝脏脂肪变性和腹部脂肪分布（通过磁共振波谱和成像评估）。测量炎症的血浆标志物以及代谢、肝脏和抗氧化功能;在外周血单核细胞中测量靶基因的转录。白藜芦醇的药代动力学和安全性assessed.Results：八周的白藜芦醇给药并没有减少胰岛素抵抗，脂肪变性，或腹部脂肪分布时，与基线相比。未观察到血浆脂质或抗氧化活性的变化。与安慰剂组相比，白藜芦醇组患者的丙氨酸和天冬氨酸转氨酶水平显着增加，直到第6周。白藜芦醇没有显着改变转录NQO 1，PTP 1B，IL 6，或HO 1在外周血单核细胞。Resveratrol was well tolerated.CONCLUSIONS：与安慰剂相比，白藜芦醇8周给药并没有显著改善NAFLD的任何特征，但它增加了肝应激，基于观察到的肝酶水平的增加。还需要进一步的研究来确定那些旨在模拟卡路里限制的药物，如白藜芦醇，是否对肥胖并发症安全有效。
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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.