The effect of tea polyphenols on chronic disease: obesity, the metabolic syndrome, and colon cancer

Abstract

The prevalence of obesity and the metabolic syndrome has more than doubled in the last 30 years. Colon cancer is the second leading cause of cancer-related death in the United States. Many studies show beneficial effects of certain dietary constituents, including green tea, in the prevention of these diseases. In the first set of experiments, I determined the effect of (-)-epigallocatechin-3-gallate (EGCG) on weight gain and related factors in a high-fat diet-induced mouse model for obesity and the metabolic syndrome. I found that l6-week treatment of 0.32% EGCG in the diet (w/w) significantly reduced body weight gain ([greater than sign]50%) and body fat percentage (by 10%) in comparison to control mice. Visceral fat weight was significantly decreased by EGCG treatment. Biochemical measurements revealed that EGCG treatment significantly attenuated insulin resistance and plasma cholesterol. Liver pathologies were significantly lessened by EGCG, as indicated by decreased liver weight, triglyceride content, and transaminase release into plasma. Plasma monocyte chemoattractant protein (MCP-1) levels were also decreased by EGCG, suggesting reduction of inflammation by EGCG. In the next set of experiments, I determined the effect of a combination of EGCG (0.16% in the drinking fluid) and fish oil in the diet (12% w/w), on intestinal tumorigenesis in ApcMin/+ mice. Combination treatment reduced tumor number by 53% compared to controls; at the doses used, neither agent alone had a significant effect. β-catenin nuclear positivity in intestinal adenomas from the combination group was lower than control mice, indicating modulation of Wnt signaling. Fish oil and the combination significantly reduced prostaglandin E2 levels in adenomas compared to controls, suggesting modulation of aberrant arachidonic acid metabolism. Akt phosphorylation in adenomas was significantly reduced in all treatment groups, which may have contributed to the observed increase in apoptosis. The results from these two studies indicate that long-term treatment with EGCG decreases risk for obesity and conditions associated with the metabolic syndrome, and that a combination of EGCG and fish oil can inhibit intestinal tumorigenesis in ApcMin/+ mice. These effects may be mediated through multiple mechanisms and should be addressed in future studies in the prevention of chronic disease.%%%%