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Ben May Institute for Cancer Research Department of Biochemistry and Molecular Biology Tang Center for Herbal Medicine Research University of Chicago Chicago, IL 60637 E-mail: sliao{at}huggins.bsd.uchicago.edu
Dear Sir:
Consumption of green tea may enhance health because it reduces the incidence of cancer in various experimental models, is a potent antioxidant, and modulates serum cholesterol concentrations (1). Green tea also has effects on body weight (2, 3) and energy expenditure (4). Dulloo et al (4) reported that 24-h energy expenditure (EE) and fat oxidation increased in healthy, young men who consumed a green tea extract containing caffeine and green tea polyphenols. Because a dose of caffeine equivalent to that found in the green tea extract did not affect 24-h EE, it was concluded that green tea polyphenols, especially the most abundant oneepigallocatechin gallate (EGCG)may stimulate thermogenesis and fat oxidation. Experimental analysis of the mechanisms by which green tea exerts its effect is difficult because green tea is a complex mixture of various phytochemicals (1) that may not be absorbed easily from the gastrointestinal tract (5). A synergistic effect of EGCG and caffeine may be responsible for enhancing thermogenesis and fat oxidation, although this was not investigated in the study by Dulloo et al.
The effects of green tea extracts on EE and fat oxidation observed in the study by Dulloo et al (4) are in contrast with the findings of our studies, in which we showed that intraperitoneal injection of EGCG (>98% pure), but not other structurally related catechinssuch as epicatechin (EC), epigallocatechin (EGC), and epicatechin gallate (ECG)caused acute body weight loss in male and female Sprague-Dawley rats within 27 d of treatment (2, 3). EGCG also significantly reduced or prevented an increase in body weight in lean (Figure 1A) and obese (Figure 1B) male (3) and female Zucker rats. The effective dose of EGCG was initially 3050 mg EGCG/kg body wt. However, these rats gradually adapted within 1 wk and higher doses of EGCG (100 mg/kg body wt) were needed to reduce or prevent increases in body weight. The loss in body weight was reversible; when EGCG administration was stopped, animals regained the lost body weight (Figure 1A). Lean and obese male Zucker rats injected intraperitoneally with 7090 mg EGCGkg body wt-1d-1 lost 1013% of their body weight relative to their initial weight and 25% of their body weight relative to the control after 8 d of treatment.
FIGURE 1. . Mean (±SEM) changes in body weight in lean (A) and obese (B) male Zucker rats and food intake in lean (C) and obese (D) male Zucker rats injected intraperitoneally daily with epigallocatechin gallate (EGCG) at doses (10-80 mg) indicated at the arrows. Open circles represent rats initially injected with phosphate-buffered saline (control) and closed circles represent rats initially injected with EGCG in phosphate-buffered saline. On day 14, a crossover involving lean rats was initiated at a dose of 15 mg EGCG, which was increased to 30 mg on day 26. Significantlly different from control, P < 0.05. n = 4-5.
The weight-loss effect of EGCG in rats may have been due to a reduction in food intake (3). Male Sprague-Dawley rats, given EGCG orally, consumed 15% less food than did the control rats and lost 5% of their initial body weight. Male and female Sprague-Dawley rats and male lean and obese Zucker rats injected intraperitoneally with EGCG consumed 5060% less food than did control rats. This effect was catechin-specific; EGCGbut not EC, EGC, or ECGresulted in a reduction in food intake in Sprague-Dawley rats. The effect of EGCG on food intake reduction (Figure 1, C and D) was independent of an intact leptin receptor because leptin receptorintact lean Zucker rats and leptin receptordefective obese Zucker rats (6) had similar responses to EGCG treatment (3). EGCG, therefore, may interact specifically with a component of the leptin receptorindependent appetite control pathway.
Dulloo et al (4) also observed that EGCG-containing green tea extracts were more potent than were equimolar concentrations of caffeine alone in stimulating in vitro the respiration rate of brown adipose tissue. Additionally, the in vitro thermogenic effect of a green tea extract on brown adipose tissue could be mimicked by EGCG. The enhanced rates of thermogenesis and respiration by green tea extracts may support our in vitro studies in which EGCG reduced the total triacylglycerol accumulation of murine 3T3-L1 preadipocytes during their differentiation to adipocytes. However, we found that EGCG also inhibited the proliferation of 3T3-L1 preadipocytes. The concentration of EGCG that inhibited proliferation by 50% was 10 µmol/L; at this concentration, EGCGbut not EC, EGC, or ECGinhibited insulin-induced increases in cell number (by 34%) and the triacylglycerol content (by 54%) during a 9-d period of differentiation. Recently, EGCG and ECG were shown to be inhibitors (50% inhibition at 0.31 mmol/L) of acetyl-CoA carboxylase activity, a rate-limiting step in the fatty acid biosynthesis pathway, in 3T3-L1 cells (7). EGCG at a dose of 10100 µmol/L could also reduce the cell number and triacylglycerol content of differentiating preadipocytes treated with dexamethasone, 1-methyl-3-isobutylxanthine, and insulin. Therefore, the in vitro effect of EGCG on fat tissues may be mediated by modulation of hormone-stimulated cell proliferation and differentiation or by inhibition of fat cell functions.
The effects of long-term daily oral consumption of 24 cups (5001000 mL) of green tea or EGCG-containing green tea extracts may mimic some of the acute effects of EGCG. Studies have shown that oral consumption of green tea, EGCG, or EGCG-containing green tea extract can lower serum and LDL cholesterol, increase HDL cholesterol, and lower serum glucose (1, 3, 8). On the basis of the in vivo effects of EGCG on body weight loss, body fat, serum lipid nutrients, thermogenesis, and fat oxidation (14, 8) and of the in vitro effects of EGCG on fat cell functions (4, 7), long-term consumption of green tea may decrease the incidence of obesity and, perhaps, green tea components such as EGCG may be useful for treating obesity. Recently, a weight-reducing effect of oolong tea (9) was observed in mice consuming a high-fat diet. It is possible that the EGCG in the oolong tea was responsible for the observed effects. Oolong tea, however, contains much less EGCG than does green tea, so it remains to be established what components of oolong tea caused the weight reduction in these mice. Studies, like ours, with purified components are necessary to identify active components.
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