Submitted to: BARC Poster Day
Publication Type: Abstract Only
Publication Acceptance Date: 3/26/2007
Publication Date: 3/30/2007
Citation: Cao, H., Urban Jr, J.F., Anderson, R.A. 2007. Prevention of obesity by plant polyphenols via tristetraprolin-mediated cytokine mrna instability. BARC Poster Day. Interpretive Summary:
Technical Abstract: Obesity, one of the most pervasive public health problems, increases the risks of developing type 2 diabetes, cardiovascular, and related diseases. Obesity is a disease of appetite regulation and energy metabolism, resulting from excess fat accumulation in adipocytes. It is associated with low levels of chronic inflammation mediated by adipocytokines and pro-inflammatory cytokines, but the mechanisms of how inflammation relates to obesity are not completely understood. Tristetraprolin (TTP), an anti-inflammatory protein, binds to clinically important mRNAs, such as tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF) mRNAs, and promotes mRNA destruction. Our hypothesis is that plant polyphenols help control obesity, in part, by increasing TTP that promotes degradation of cytokine mRNAs involved in obesity. Mouse 3T3-L1 adipocytes were differentiated, following induction with insulin and steroid hormone, as judged by microscopic observation of fat accumulation in the adipocytes and detection of adipocyte-specific gene expression by real-time PCR assays. TTP gene expression was induced by insulin and cinnamon polyphenols in mouse adipocytes, resulting in decreases in VEGF gene expression. In addition, a polyphenolic extract from green tea also increased TTP gene expression in liver and muscle of rats fed a high fructose diet to induce the metabolic syndrome. Green tea polyphenolic extract also decreased TNF and COX2 gene expression in the liver and muscle. Based on these results, we propose a mechanism to link plant polyphenols, insulin, TTP, and cytokines in the regulation of obesity. This work leads to a better understanding of the regulation of mRNA stability in fat cells and provides information linking TTP in the regulation of obesity.