MINORITY PREDOCTORAL FELLOWSHIP PROGRAM

描述(由申请人提供)：这项研究项目的长期目标是确定控制人类肥胖的新饮食策略，肥胖是美国最普遍的营养相关疾病。这项应用的目的是识别共轭亚油酸(CLA)的异构体产生的上游信号，CLA是牛肉和乳制品以及减肥膳食补充剂中发现的脂肪酸，它激活导致脂肪细胞脱脂的细胞信号。为了完成这一目标，将在人脂肪细胞培养中实现以下特定目标：目的1)确定蛋白激酶C(PKC)在介导CLA激活核因子KB(NFKB)和细胞外信号调节激酶(ERK)1/2和脱脂中的作用；目的2)确定CLA增加[Ca+]i的机制及其对NFKB和ERK1/2信号和脱脂的影响；以及目的#3)确定CLA增加脂代谢酶活性的程度，产生激活NFKB和ERK1/2并促进脱脂的信号。从这项提案中获得的数据有望为制定预防和治疗肥胖症和II型糖尿病的治疗目标提供重要的见解，并降低与肥胖症相关的医疗成本。

DESCRIPTION (provided by applicant): The long-term goal of this research project is to identify novel dietary strategies for controlling human obesity, the most prevalent nutritional-related disease in America. The objective of this application is to identify upstream signals produced by an isomer of conjugated linoleic acid (CLA), fatty acids found in beef and dairy products and in dietary supplements for weight loss, that activate cell signals that lead to adipocyte delipidation. To complete this objective, the following specific aims will be carried out in cultures of human adipocytes: Aim #1) Determine the role of protein kinase C (PKC) in mediating CLA's activation of nuclear factor KB (NFKB) and extracellular signal-regulated kinase kinase (ERK)1/2 and delipidation; Aim #2) Identify the mechanism by which CLA increases [Ca2+]i, and its impact on NFKB and ERK1/2 signaling and delipidation; and Aim #3) Determine the extent to which CLA increases the activities of lipid metabolizing enzymes, generating signals that activate NFKB and ERK1/2 and promote delipidation. Data attained from this proposal are expected to provide critical insight for the development of therapeutic targets for the prevention and treatment of obesity and type II diabetes, and reduce health care costs related to obesity.