ACT 2 PROJ 2: LONGEVITY FOODS AND OBESITY-ASSOCIATED INSULIN RESISTANCE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 肥胖症在美国已经达到流行的程度，并与2型糖尿病和心血管疾病(CVD)密切相关，这导致卫生局局长呼吁全国努力不仅要确定肥胖症的原因，而且要概述有效的和文化上合适的干预措施。由于无法维持长期的减肥，目前治疗肥胖症的疗效复杂，而治疗2型糖尿病的方法容易出现药物-药物相互作用和各种副作用，如额外的体重增加和继发性失败。有趣的是，在冲绳日本人中，糖尿病和心脏病等慢性病的发病率只有美国人的五分之一。在各种生活方式因素中，卡路里摄入量较低，水果和蔬菜消费量较高。这项研究的长期目标是调查药用/功能食品预防和/或改善肥胖相关的胰岛素抵抗、糖尿病血脂异常和心血管疾病的效果，并确定潜在的机制。该项目旨在利用亚洲蔬菜苦瓜(Momordica Charantia，BM)，确定特定的分子靶点，并描述改善肥胖相关胰岛素抵抗的机制。该项目的具体目的是：1)研究苦瓜汁对小鼠脂肪细胞Sirt1激活、PPARy抑制和FOXO调节的影响；2)研究苦瓜汁对小鼠体内FOXO调节的影响；3)进行可行性和中试喂养研究，以测试苦瓜汁对正常人体的影响。目的1将在小鼠脂肪细胞培养中进行研究，并将通过siRNA研究来研究BM对Sirt1调控的特异性。目的2采用本实验室建立的高脂饮食(HFD)-小鼠模型进行研究。我们希望将体外和体内研究的结果转化为对患有肥胖症和/或2型糖尿病的少数民族人群的临床试验。这类研究可能会对可纳入日常饮食的治疗方案的开发产生重大影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Obesity has reached epidemic proportions in the United States and is closely linked to type 2 diabetes and cardiovascular disease (CVD), leading the Surgeon General to issue a call for a national effort not only to identify the causes of obesity, but also to outline effective and culturally appropriate interventions. Efficacies of current therapies for obesity are complicated due to inability to maintain long-term weight loss, while those for type 2 diabetes are prone to drug-drug interactions and various side effects, such as additional weight gain and secondary failure. Interestingly, the occurrence of chronic diseases, such as diabetes and heart disease, among Okinawan Japanese is only one fifth that of Americans. Among the various lifestyle factors are lower calorie intake and high consumption of fruits and vegetables. The long-term goal of this research is to investigate the efficacy of medicinal/functional foods to prevent and/or ameliorate obesity-associated insulin resistance, diabetic dyslipidemia and CVDs, and to identify the underlying mechanisms. This project aims to identify specific molecular targets and delineate the mechanisms involved in ameliorating obesity-associated insulin resistance, using Momordica charantia (bitter melon, BM), an Asian vegetable. The specific aims of the project are to: 1) investigate the effects of bitter melon juice-associated Sirt1 activation, PPARy repression and Foxo regulation in mouse adipocytes; 2) investigate the in vivo effects of bitter melon juice on Foxo regulation in mice; and 3) conduct feasibility and pilot-feeding studies to test the effects of bitter melon in normal human subjects. Aim 1 will be investigated in mouse adipocyte cultures and the specificity of Sirt1 regulation by BM will be investigated using siRNA studies. Aim 2 will be investigated using the high fat diet (HFD)-mouse model established in our laboratory. We expect to translate the results of the in vitro and in vivo studies to clinical trials among minority populations with obesity and/or type 2 diabetes mellitus. Such studies may have a significant impact on the development of therapeutic regimens that can be incorporated into the daily diet.