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. ? ? ?
