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

点击翻译按钮获取中文摘要

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 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 cardiovascular diseases (CVD), and identify the underlying mechanisms. The objective of this project is 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, while Aim 3 will test the translation of our basic science observations in human subjects. We expect to translate the results of the in vitro and in vivo study 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.