Xanthohumol and 8-prenylnaringenin ameliorate diabetic-related metabolic dysfunctions in mice
Xanthohumol and 8-prenylnaringenin ameliorate diabetic-related metabolic dysfunctions in mice
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DOI：
10.1016/j.jnutbio.2017.03.006
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发表时间：
2017-07-01
影响因子：
5.6
通讯作者：
Soares, Raquel
中科院分区：
文献类型：
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作者：
Costa, Raquel;Rodrigues, Ilda;Soares, Raquel
2 型糖尿病 (T2DM) 是一种以特定组织代谢紊乱为特征的慢性疾病。本研究旨在分析黄腐酚 (XN) 和 8-异戊二烯柚皮素 (8PN) 这两种啤酒衍生多酚对 T2DM 小鼠模型肝脏和骨骼肌脂质和糖酵解代谢的影响。将30只C5781/6小鼠随机分为5组：标准饮食（对照）、高脂饮食（DM）、高脂饮食加乙醇（DM-Ethanol）、高脂饮食加10 mg/L XN（DM-XN）和高脂饮食加10 mg/L 8PN（DM-8PN），持续20周。处死前1周进行空腹血糖和胰岛素耐量测试。研究结束时，收集血液、肝脏和骨骼肌。 XN 和 8PN 治疗均可防止体重增加；降低血糖、甘油三酯、胆固醇和碱性磷酸酶水平；并改善胰岛素敏感性。多酚促进肝脏和骨骼肌 AMP 激活蛋白激酶 (AMPK) 的激活，减少目标脂肪生成酶（甾醇调节元件结合蛋白-1c 和脂肪酸合酶）和乙酰辅酶 A 羧化酶活性的表达。此外，XN 和 8PN 治疗均降低了参与脂肪酸摄取的 VEGFR-1/VEGFB 途径，并增加了参与 GLUT4 膜易位的 AS160 表达。所提供的数据表明，XN 和 8PN 治疗都会导致 AMPK 信号通路激活，从而抑制脂肪生成。食用它们可以防止体重增加并改善血脂状况，并显着改善胰岛素抵抗和葡萄糖耐量。富含 XN 或 8PN 的饮食可以通过调节葡萄糖和脂质途径来改善糖尿病相关的代谢紊乱。 (C) 2017 Elsevier Inc. 保留所有权利。
Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by metabolic disturbances in specific tissues. The present work aimed to analyze the effects of xanthohumol (XN) and 8-prenylnaringenin (8PN), two beer-derived polyphenols, in liver and skeletal muscle lipid and glycolytic metabolism in T2DM mice model. Thirty C5781/6 mice were randomly divided into five groups: standard diet (control), high-fat diet (DM), high-fat diet plus ethanol (DM-Ethanol), high-fat diet plus 10 mg/L XN (DM-XN) and high-fat diet plus 10 mg/L 8PN (DM-8PN) during 20 weeks. Fasting blood glucose and insulin tolerance tests were performed 1 week before sacrifice. At the end of the study, blood, liver and skeletal muscle were collected. Both XN and 8PN treatments prevented body weight gain; decreased glycemia, triglyceride, cholesterol and alkaline phosphatase levels; and improved insulin sensitivity. Polyphenols promoted hepatic and skeletal muscle AMP-activated protein kinase (AMPK) activation, diminishing the expression of target lipogenic enzymes (sterol regulatory element binding protein-1c and fatty acid synthase) and acetyl-CoA carboxylase activity. Moreover, both XN and 8PN treatments decreased VEGFR-1/VEGFB pathway, involved in fatty acid uptake, and increased AS160 expression, involved in GLUT4 membrane translocation. Presented data demonstrated that both XN and 8PN treatment resulted in AMPK signaling pathway activation, thus suppressing lipogenesis. Their consumption prevented body weight gain and improved plasma lipid profile, with significant improvement of insulin resistance and glucose tolerance. XN- or 8PN-enriched diet could ameliorate diabetic-associated metabolic disturbances by regulating glucose and lipid pathways. (C) 2017 Elsevier Inc. All rights reserved.