Cruciferous Indoles in the Amelioration of the Metabolic Syndrome

描述(申请人提供)：这项研究的目标是提供可靠的科学证据，证明十字花科吲哚化合物在预防和治疗心血管疾病(CVD)中潜在的健康益处。食用十字花科蔬菜的人心血管疾病(CVD)的重要危险因素的患病率较低，包括高脂血症、肥胖症和2型糖尿病。尽管有这些发现，但对于调节这种健康益处的机制，特别是代谢综合征--一种正在出现的严重公共卫生问题--几乎完全缺乏了解。这一机制可能是由吲哚类化合物介导的，吲哚类化合物在十字花科蔬菜中特别丰富和独特。本实验室关于十字花科吲哚对脂质代谢的有利作用的最新发现，以及我们实验室最近建立的胰岛素抵抗和代谢紊乱的仓鼠模型，可能会揭示十字花科吲哚在治疗代谢紊乱和潜在的胰岛素抵抗方面的新作用。利用胰岛素抵抗的仓鼠模型，我们假设补充十字花科吲哚将通过一些机制逆转代谢性高脂血症。我们进一步假设，补充十字花科吲哚将改善胰岛素抵抗。如果我们的化合物被证明具有降血脂作用和改善糖代谢，将调查两个重要的转录因子(PPAR和SREBP)的参与。我们将使用已建立的胰岛素抵抗动物模型，通过评估吲哚-3-甲醇(I-3-C)(一种常见的吲哚补充剂)的效果来检验这些假设。我们相信这项研究是重要的，因为它将为吲哚补充剂的健康声明增加新的科学有效性，这可能导致人类饮食干预试验。寻找有关现有补充和替代医学临床模式的新信息是NIH-NCCAM计划的一个重要目标。2型糖尿病患者死亡的主要原因是心血管疾病(CVD)。2型糖尿病与心血管疾病之间的密切联系可能与血脂异常有关。我们的研究涉及阐明来自十字花科蔬菜的微量营养素如何有益于治疗与2型糖尿病相关的血脂异常。

DESCRIPTION (provided by applicant): The goal of this research is to provide sound scientific evidence of the potential health benefit of cruciferous indole compounds in the prevention and treatment of cardiovascular disease (CVD). People who consume cruciferous vegetables have a lower prevalence of important risk factors for cardiovascular disease (CVD), including hyperlipidemia, obesity, and type 2 diabetes. Despite these findings, there is an almost complete absence of knowledge on the mechanisms that mediate this health benefit, particularly on the metabolic syndrome - a serious emerging public health concern. It is probable that the mechanism may be mediated by indolic compounds that are particularly rich and distinct in cruciferous vegetables. The recent findings in our laboratory on the favorable effects of cruciferous indoles on lipid metabolism and the recent development of a hamster model of insulin resistance and metabolic dyslipidemia in our laboratory could potentially unveil a new role for cruciferous indoles in the treatment of the metabolic dyslipidemia and potentially insulin resistance. Using a hamster model of insulin resistance, we hypothesize that supplementation of cruciferous indoles will reverse the metabolic hyperlipidemia through a number of mechanisms. We further hypothesize that supplementation of cruciferous indoles will ameliorate insulin resistance. Should our compound be shown to exert a hypolipidemic effect and improve glucose metabolism, the involvement of two important transcription factors (PPAR and SREBP) will be investigated. We will test these hypotheses by assessing the effects of indole-3-carbinol (I-3-C), a common indole supplement, using an established animal model of insulin resistance. We believe this study is important as it will add new scientific validity to health claims for indole supplements which could lead to human dietary intervention trials. Finding new information about existing complementary and alternative medicine clinical modalities is an important goal of the NIH-NCCAM program. The leading cause of mortality in people with type 2 diabetes is cardiovascular disease (CVD). The close association between type 2 diabetes and CVD may be due to lipid abnormalities. Our study involves the elucidation of how micronutrients from cruciferous vegetables may be beneficial in treating the lipid abnormality associated with type 2 diabetes.