Costa Raquel, Rodrigues Ilda, Guardão Luísa, Rocha-Rodrigues Sílvia, Silva Carolina, Magalhães José, Ferreira-de-Almeida Manuel, Negrão Rita, Soares Raquel
Department of Biochemistry, Faculty of Medicine of the University of Porto, Porto, Portugal; i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
Department of Biochemistry, Faculty of Medicine of the University of Porto, Porto, Portugal.
J Nutr Biochem. 2017 Jul;45:39-47. doi: 10.1016/j.jnutbio.2017.03.006. Epub 2017 Apr 6.
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 C57Bl/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.
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。本研究旨在分析两种啤酒衍生的多酚——黄腐酚（XN）和8-异戊烯基柚皮素（8PN）对T2DM小鼠模型肝脏和骨骼肌脂质及糖酵解代谢的影响。将30只C57Bl/6小鼠随机分为五组：标准饮食组（对照组）、高脂饮食组（DM组）、高脂饮食加乙醇组（DM-乙醇组）、高脂饮食加10 mg/L XN组（DM-XN组）和高脂饮食加10 mg/L 8PN组（DM-8PN组），持续20周。在处死前1周进行空腹血糖和胰岛素耐量试验。研究结束时，采集血液、肝脏和骨骼肌样本。XN和8PN处理均能防止体重增加；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中AMP激活的蛋白激酶（AMPK）活化，减少靶标脂肪生成酶（固醇调节元件结合蛋白-1c和脂肪酸合酶）的表达以及乙酰辅酶A羧化酶活性。此外，XN和8PN处理均降低了参与脂肪酸摄取的VEGFR-1/VEGFB通路，并增加了参与GLUT4膜转位的AS160表达。现有数据表明，XN和8PN处理均导致AMPK信号通路活化，从而抑制脂肪生成。它们的摄入可防止体重增加并改善血浆脂质谱，显著改善胰岛素抵抗和葡萄糖耐量。富含XN或8PN的饮食可通过调节葡萄糖和脂质途径改善糖尿病相关的代谢紊乱。
