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. ? ? ?
