Department of Plant Biology and Pathology, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, United States of America.
PLoS One. 2011;6(10):e24634. doi: 10.1371/journal.pone.0024634. Epub 2011 Oct 10.
Obesity is a major and independent risk factor for cardiovascular disease and it is strongly associated with the development of dyslipidemia, insulin resistance and type 2 diabetes. Flavonoids, a diverse group of polyphenol compounds of plant origin widely distributed in human diet, have been reported to have numerous health benefits, although the mechanisms underlying these effects have remained obscure. We analyzed the effects of chronic dietary supplementation with flavonoids extracted from cranberry (FLS) in normal and obese C57/BL6 mice compared to mice maintained on the same diets lacking FLS. Obese mice supplemented with flavonoids showed an amelioration of insulin resistance and plasma lipid profile, and a reduction of visceral fat mass. We provide evidence that the adiponectin-AMPK pathway is the main mediator of the improvement of these metabolic disorders. In contrast, the reduced plasma atherogenic cholesterol observed in normal mice under FLS seems to be due to a downregulation of the hepatic cholesterol synthesis pathway. Overall, we demonstrate for the first time that the molecular mechanisms underlying the beneficial effects of flavonoids are determined by the metabolic state.
肥胖是心血管疾病的一个主要且独立的危险因素，它与血脂异常、胰岛素抵抗和 2 型糖尿病的发展密切相关。类黄酮是植物来源的一类多酚化合物，广泛存在于人类饮食中，据报道具有多种健康益处，尽管这些作用的机制仍不清楚。我们分析了在正常和肥胖 C57/BL6 小鼠以及在缺乏 FLS 的相同饮食中维持的小鼠中，长期饮食补充从蔓越莓中提取的类黄酮（FLS）的效果。补充类黄酮的肥胖小鼠表现出胰岛素抵抗和血浆脂质谱的改善，以及内脏脂肪量的减少。我们提供的证据表明，脂联素-AMPK 途径是改善这些代谢紊乱的主要介导者。相比之下，在 FLS 下正常小鼠中观察到的降低的血浆动脉粥样硬化胆固醇似乎是由于肝脏胆固醇合成途径的下调。总的来说，我们首次证明了类黄酮有益作用的分子机制取决于代谢状态。
