Green tea (Camellia sinensis, Theaceace) is the second most popular beverage in the world and has been extensively studied for its putative disease preventive effects. Green tea is characterized by the presence of a high concentrations of polyphenolic compounds known as catechins, with (−)-epigallocatechin-3-gallate (EGCG) being the most abundant and most well-studied. Metabolic syndrome (MetS) is a complex condition that is defined by the presence of elevated waist circumference, dysglycemia, elevated blood pressure, decrease serum high density lipoprotein-associated cholesterol, and increased serum triglycerides. Studies in both in vitro and laboratory animal models have examined the preventive effects of green tea and EGCG against the symptoms of MetS. Overall, the results of these studies have been promising and demonstrate that green tea and EGCG have preventive effects in both genetic and dietary models of obesity, insulin resistance, hypertension, and hypercholesterolemia. Various mechanisms have been proposed based on these studies and include: modulation of dietary fat absorption and metabolism, increased glucose utilization, decreased de novo lipogenesis, enhanced vascular responsiveness, and antioxidative effects. In the present review, we discuss the current state of the science with regard to laboratory studies on green tea and MetS. We attempt to critically evaluate the available data and point out areas for future research. Although there is a considerable amount of data available, questions remain in terms of the primary mechanism(s) of action, the dose-response relationships involved, and the best way to translate the results to human intervention studies.

Tea (Camellia sinensis, Theaceae) and tea polyphenols have been studied for the prevention of chronic diseases, including obesity. Obesity currently affects >20% of adults in the United States and is a risk factor for chronic diseases such as type II diabetes, cardiovascular disease, and cancer. Given this increasing public health concern, the use of dietary agents for the prevention of obesity would be of tremendous benefit. Whereas many laboratory studies have demonstrated the potential efficacy of green or black tea for the prevention of obesity, the underlying mechanisms remain unclear. The results of human intervention studies are mixed and the role of caffeine has not been clearly established. Finally, there is emerging evidence that high doses of tea polyphenols may have adverse side effects. Given that the results of scientific studies on dietary components, including tea polyphenols, are often translated into dietary supplements, understanding the potential toxicities of the tea polyphenols is critical to understanding their potential usefulness in preventing obesity. In this review, we will critically evaluate the evidence for the prevention of obesity by tea, discuss the relevance of proposed mechanisms in light of tea polyphenol bioavailability, and review the reports concerning the toxic effects of high doses of tea polyphenols and the implication that this has for the potential use of tea for the prevention of obesity. We hope that this review will expose areas for further study and encourage research on this important public health issue.

(−)-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, has been shown to prevent the development of obesity in rodent models. Here, we examined the effect of EGCG on markers of fat oxidation in high fat-fed C57bl/6J mice. High fat-fed mice treated with 0.32% dietary EGCG for 16 weeks had reduced body weight gain and final body weight (19.2% and 9.4%, respectively) compared to high fat-fed controls. EGCG-treatment decreased fasting blood glucose, plasma insulin, and insulin resistance by 18.5%, 25.3%, and 33.9%, respectively. EGCG treatment also reduced markers of obesity-related fatty liver disease in high fat-fed mice. Gene expression analysis of skeletal muscle showed that EGCG increased mRNA levels of nuclear respiratory factor (nrf)1, medium chain acyl coA decarboxylase (mcad), uncoupling protein (ucp)3, and peroxisome proliferator responsive element (ppar)α by 1.4 – 1.9-fold compared to high fat-fed controls. These genes are all related to mitochondrial fatty acid oxidation. In addition, EGCG increased fecal excretion of lipids in high fat-fed mice. In summary, it appears that EGCG modulates body weight gain in high fat-fed mice both by increasing the expression of genes related fat oxidation in the skeletal muscle and by modulating fat absorption from the diet.

Tea (Camellia sinensis, Theaceae) has been shown to have obesity preventive effects in laboratory studies. We hypothesized that dietary epigallocatechin‐3‐gallate (EGCG) could reverse metabolic syndrome in high fat‐fed obese C57bl/6J mice, and that these effects were related to inhibition of pancreatic lipase (PL). Following treatment with 0.32% EGCG for 6 weeks, a 44% decrease in body weight (BW) gain in high fat‐fed, obese mice (P < 0.01) was observed compared to controls. EGCG treatment increased fecal lipid content by 29.4% (P < 0.05) compared to high fat‐fed control, whereas in vitro, EGCG dose‐dependently inhibited PL (IC50 = 7.5 µmol/l) in a noncompetitive manner with respect to substrate concentration. (−)−Epicatechin‐3‐gallate exhibited similar inhibitory activity, whereas the nonester‐containing (−)−epigallocatechin did not. In conclusion, EGCG supplementation reduced final BW and BW gain in obese mice, and some of these effects may be due to inhibition of PL by EGCG.

Few studies have examined the effect of black tea (Camellia sinensis) theaflavins on obesity-related targets. Pancreatic lipase (PL) plays a central role in fat metabolism and is a validated target for weight loss. We compared the inhibitory efficacy of individual theaflavins and explored the underlying mechanism. Theaflavin-3,3′-digallate (TFdiG), theaflavin-3′-gallate, theaflavin-3-gallate, and theaflavin inhibited PL with IC50 of 1.9, 4.2, 3.0, and >10 μmol/L. The presence and location of the galloyl ester moiety were essential for inhibitory potency. TFdiG exhibited mixed inhibition with respect to substrate concentration. In silico modeling showed that theaflavins bind to Asn263 and Asp206, which form a pocket adjacent to the active site, and galloyl-containing theaflavins are then predicted to perturb the protonation of His264. These data provide a putative mechanism to explain the anti-obesity effects of tea.

Tea (Camellia sinensis) has shown anti‐obesity effects in animals. Tea polyphenols can inhibit digestive enzymes such as pancreatic lipase (PL), phospholipase A2 (PLA2), and trypsin in vitro. Our objective was to explore the mechanisms of inhibition by tea polyphenols by enzymology and in silico modeling. Theaflavin‐3,3’‐digallate (TFdiG), theaflavin‐3’‐gallate, theaflavin‐3‐gallate, and theaflavin inhibit PL with IC50 = 1.9, 4.2, 3.0, and 32.9 µM, respectively, indicating that the location of the galloyl ester is essential for inhibitory potency. TFdiG exhibits a mixed mode of inhibition. Theaflavins were found to bind to a pocket adjacent to the active site in PL; galloyl‐containing theaflavins are able to form a hydrogen bond with His264, which forms part of the catalytic triad. Similar interactions are predicted with green tea catechins. Catechins also inhibit PLA2. Modeling studies show that these compounds occupy a tunnel that leads to the active site and are stabilized by van der Waals bonds. This interaction is expected to result in noncompetitive inhibition. We found that (‐)‐epigallocatechin‐3‐gallate (EGCG) inhibited trypsin (IC50 = 193 µM) in a non‐competitive manner. Modeling studies show that EGCG interacts with amino acids around the active site and hinders substrate binding. These findings provide insight into the mechanisms by which tea polyphenols can inhibit key digestive enzymes. Grant Funding Source: NIH AT004678

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