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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 肥胖在美国已达到流行病的程度，并与2型糖尿病和心血管疾病（CVD）密切相关，导致外科医生发出呼吁，要求全国努力不仅要确定肥胖的原因，还要概述有效和文化上适当的干预措施。目前肥胖症治疗的有效性是复杂的，因为无法保持长期的体重减轻，而那些2型糖尿病容易发生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，冲绳日本人的糖尿病和心脏病等慢性病发病率仅为美国人的五分之一。在各种生活方式因素中，低热量摄入和高水果和蔬菜消费。本研究的长期目标是研究药用/功能性食品预防和/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功效，并确定潜在的机制。该项目旨在确定特定的分子靶点，并描述改善肥胖相关的胰岛素抵抗的机制，使用苦瓜（苦瓜，BM），一种亚洲蔬菜。该项目的具体目标是：1）研究苦瓜汁相关的Sirt 1激活，PPARy抑制和Foxo调节在小鼠脂肪细胞中的作用; 2）研究苦瓜汁对小鼠Foxo调节的体内作用; 3）进行可行性和中试喂养研究，以测试苦瓜在正常人类受试者中的作用。目的1将在小鼠脂肪细胞培养物中进行研究，并将使用siRNA研究BM对Sirt 1调节的特异性。目的二是利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肥胖和/或2型糖尿病少数人群的临床试验。这些研究可能会对制定可纳入日常饮食的治疗方案产生重大影响。

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.