Journal of Ethnopharmacology 104 (2006) 24–31 Green tea leaf extract improves lipid and glucose homeostasis in a fructose-fed insulin-resistant hamster model Rachel W. Li a , Teresa D. Douglas a , Geoffrey K. Maiyoh a , Khosrow Adeli b , Andre G. Theriault a,∗ a Division of Medical Technology, John A. Burns School of Medicine, University of Hawaii at Manoa, Bio C-206, 1960 East-West Road, Honolulu, HI 96822, USA b Department of Laboratory Medicine, The Hospital for Sick Children, Toronto, Canada M5G 1X8 Received 21 March 2005; received in revised form 11 August 2005; accepted 12 August 2005 Available online 3 October 2005 Abstract The present study evaluated the effect of green tea (Camellia sinensis L.) leaf extract on triglyceride and glucose homeostasis in a fructose-fed hypertriglyceridemic, insulin-resistant hamster model. There was a significant decrease in plasma triglyceride levels following supplementation of the green tea epigallocatechin gallate-enriched extract (42% at 150 mg/(kg day) to 62% at 300 mg/(kg day) for 4 weeks). Compared to baseline, the fructose control group at the end of the study showed elevated serum insulin and apolipoprotein B levels, and decreased serum adiponectin levels. The fructose/green tea extract group showed a reversal in all of these metabolic defects, including an improvement in glucose levels during a glucose tolerance test. Triglyceride content was also examined in various tissues and compared to the control fructose group; supplementation of the green tea extract (300mg/kg) reduced triglyceride content in liver and heart tissues. There was molecular evidence of improved lipid and glucose homeostasis based on peroxisome proliferator-activated receptor (PPAR) protein expression. Compared to the control fructose group, supplementation of the green tea extract (300 mg/kg) significantly increased PPAR and PPAR protein expression. In summary, the data suggest that intake of the green tea extract ameliorated the fructose-induced hypertriglyceridemia and the insulin-resistant state in part through PPAR. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Green tea; Insulin resistance; Triglyceride; Fructose; Peroxisome proliferator-activated receptor 1. Introduction The insulin resistance syndrome, also known as the metabolic syndrome, is a common pathophysiological condition that is implicated in the development of type 2 diabetes, atheroscle- rosis, dyslipidemia, and hypertension. The leading cause of mortality in people with the metabolic syndrome is cardiovas- cular disease (CVD) (Lakka et al., 2002). The close association Abbreviations: apoB, apolipoprotein B; BSA, bovine serum albu- min; CAD, coronary artery disease; CVD, cardiovascular disease; EGCG, (-)epigallocatechin gallate; ELISA, enzyme-linked immunosorbent assay; GLUT IV, glucose transporter IV; HDL, high-density lipoprotein; HRP, horseradish peroxidase; i.p. GTT, intraperitoneal glucose tolerance test; LDH, lactate dehydrogenase; LDL, low-density lipoprotein; PPAR, peroxisome proliferator-activated receptor; TG, triglyceride; VLDL, very low-density lipoprotein ∗ Corresponding author. Tel.: +1 808 956 8656; fax: +1 808 956 5457. E-mail address: andret@hawaii.edu (A.G. Theriault). between the metabolic syndrome and CVD may be due to the dyslipidemia. The dyslipidemia observed in the metabolic syn- drome is characterized in part by high plasma triglycerides and low high-density lipoprotein (HDL)-cholesterol concentrations (reviewed in Kohen-Avramoglu et al., 2003). Although we have made major strides in treating the dyslipi- demia associated with type 2 diabetes with both lipid-lowering and anti-diabetic drugs (Krauss and Siri, 2004), there is contin- ued controversy on what constitute the optimal diet in treating this disorder. Other than unsaturated fats and fiber (Carson, 2003), little is known of what nutrients may be beneficial in treating metabolic dyslipidemia. There is growing evidence that green tea (from the plant Camellia sinensis L. (Theaceae)) may be used to treat metabolic dyslipidemia. Animal studies have shown that green tea intake can modulate lipid metabolism in a number of diabetic animal models (Yang et al., 2001; Hasegawa et al., 2003; Wu et al., 2004). Furthermore, human intervention studies have shown that tea consumption reduces lipid levels; 0378-8741/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2005.08.045