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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31DK076208-03
Application #
7467917
Study Section
Special Emphasis Panel (ZRG1-IMM-L (29))
Program Officer
Agodoa, Lawrence Y
Project Start
2006-07-15
Project End
2009-05-31
Budget Start
2008-07-15
Budget End
2009-05-31
Support Year
3
Fiscal Year
2008
Total Cost
$25,038
Indirect Cost
Name
University of North Carolina Greensboro
Department
Nutrition
Type
Schools of Arts and Sciences
DUNS #
616152567
City
Greensboro
State
NC
Country
United States
Zip Code
27402
Shen, Wan; McIntosh, Michael K (2016) Nutrient Regulation: Conjugated Linoleic Acid's Inflammatory and Browning Properties in Adipose Tissue. Annu Rev Nutr 36:183-210
Martinez, Kristina; Shyamasundar, Shruthi; Kennedy, Arion et al. (2013) Diacylglycerol kinase inhibitor R59022 attenuates conjugated linoleic acid-mediated inflammation in human adipocytes. J Lipid Res 54:662-70
Martinez, Kristina; Kennedy, Arion; McIntosh, Michael K (2011) JNK inhibition by SP600125 attenuates trans-10, cis-12 conjugated linoleic acid-mediated regulation of inflammatory and lipogenic gene expression. Lipids 46:885-92
Kennedy, Arion; Martinez, Kristina; Schmidt, Soren et al. (2010) Antiobesity mechanisms of action of conjugated linoleic acid. J Nutr Biochem 21:171-9
Kennedy, Arion; Martinez, Kristina; Chung, Soonkyu et al. (2010) Inflammation and insulin resistance induced by trans-10, cis-12 conjugated linoleic acid depend on intracellular calcium levels in primary cultures of human adipocytes. J Lipid Res 51:1906-17
Kennedy, Arion; Overman, Angel; Lapoint, Kathleen et al. (2009) Conjugated linoleic acid-mediated inflammation and insulin resistance in human adipocytes are attenuated by resveratrol. J Lipid Res 50:225-32
Kennedy, Arion; Chung, Soonkyu; LaPoint, Kathleen et al. (2008) Trans-10, cis-12 conjugated linoleic acid antagonizes ligand-dependent PPARgamma activity in primary cultures of human adipocytes. J Nutr 138:455-61