The incidence of nonalcoholic fatty liver disease (NAFLD) has risen along with the ongoing obesity epidemic. Green tea extract (GTE) inhibits intestinal lipid absorption and may regulate hepatic lipid accumulation. The objective of this study was to determine whether GTE protects against hepatic lipid accumulation during the development of NAFLD in an obese mouse model. Five-wk-old ob/ob (obese) mice and their lean littermates (8 mice x genotype(-1) x dietary treatment(-1)) were fed GTE at 0, 1, or 2% (wt:wt) for 6 wk. The body weights of obese mice and lean littermates fed diets containing GTE were 23-25% and 11-20% lower (P < 0.05) than their respective controls fed no GTE. Histologic evaluation showed a significant reduction in hepatic steatosis in GTE-fed obese mice only and histologic scores were correlated with hepatic lipid concentration (r = 0.84; P < 0.05), which was reduced dose dependently by GTE. GTE protected against hepatic injury as suggested by 30-41% and 22-33% lower serum alanine aminotransferase and aspartate aminotransferase activities, respectively. Hepatic alpha-tocopherol was 36% higher in obese mice than lean mice. GTE tended (P = 0.06) to lower hepatic alpha-tocopherol, which was not fully explained by the GTE-mediated reduction in hepatic lipid. Hepatic ascorbic acid was lower in obese mice than in lean mice (P < 0.05) and was unaltered by GTE. Obese mice had lower serum adiponectin than lean mice and this was not affected by GTE. The results suggest that GTE protects against NAFLD by limiting hepatic lipid accumulation and injury without affecting hepatic antioxidant status and adiponectin-mediated lipid metabolism. Further study is underway to define the events by which GTE protects against obesity-triggered NAFLD.

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Oxidative stress and excess hepatic lipid are implicated in nonalcoholic fatty liver disease. Based on our previous observation that GTE attenuated hepatic lipid accumulation and injury, we hypothesized that GTE would decrease hepatic oxidative stress. Obese mice (ob/ob, n = 38) were fed a diet containing 0, 0.5 or 1% GTE for 6 wk. Lean mice, as a control, were fed 0% GTE. Serum ALT was 7.3‐times higher (p < 0.05) in obese compared to lean mice and GTE at 0.5 or 1% attenuated it by 25%. Obese mice, compared to lean mice, had greater oxidative stress as suggested by 16% lower hepatic total glutathione (tGSH) and 40% higher malondialdehyde (MDA). tGSH in obese mice fed GTE at 1% was increased to that observed in lean mice. Hepatic MDA in obese mice fed GTE at 0.5 or 1% was 16‐22% lower (p < 0.05) than in obese controls. Obese mice had 2.3‐times greater (p < 0.05) hepatic total lipid (TL) compared to lean mice which was lowered by 13% in obese mice fed GTE at 1%. This effect was consistent with hepatic triglyceride (TG) and total cholesterol (TC). Alterations in lipogenic gene expression may be involved in the hepatic lipid lowering effect of GTE. ALT was correlated (p < 0.05) to tGSH (r = ‐0.339) and MDA (r = 0.358), as well as TL (r = 0.895), TG (r = 0.777) and TC (r = 0.634). The data suggest that GTE attenuates hepatic injury by inhibiting lipid accumulation and decreasing oxidative stress. Supported by USDA NRI (2007‐02303) to RSB.

Steatotic livers are vulnerable to oxidative insults that lead to hepatic lipid peroxidation and injury. Based on our finding that green tea extract (GTE) protected against hepatic steatosis and injury, we hypothesized that GTE would decrease hepatic lipid peroxidation and inflammation. Obese (ob/ob) mice (n = 38) were fed a diet containing GTE at 0, 0.5, or 1%, and lean mice (n = 12) were fed 0% GTE for 6‐wk. Then, hepatic lipid and malondialdehyde (MDA), serum alanine aminotransferase (ALT), and inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)‐α were measured. Body weight was 33% greater (p<0.05) in obese compared to lean controls and was 18% lower in obese mice fed GTE at 1%. Hepatic lipid was 2.3‐times higher in obese mice and GTE at 1% reduced it by 13%. Hepatic MDA was 40% higher in obese compared to lean mice and GTE reduced it 16‐22%. Serum ALT was 7.3‐fold higher in obese controls and GTE at 1% decreased it 25%. MDA was correlated (p < 0.05) to ALT (r = 0.358) and total lipid (r = 0.383). Immunohistochemical evidence suggested that obese mice had greater hepatic iNOS expression and may be decreased with GTE at 1%. TNF‐α expression was unaffected by GTE. These data suggest that GTE protects against hepatic injury by decreasing hepatic lipid accumulation, peroxidation, and potentially obesity‐induced inflammation. Supported by a USDA‐NRI grant (2007‐02303) to RSB.Grant Funding SourceUSDA

GTE contains catechins and may protect against oxidative stress implicated in NAFLD. We hypothesized that GTE would protect against NAFLD by regulating hepatic enzymatic antioxidant (AOX) defenses. We fed 5‐wk old obese mice (ob/ob; n = 38) a diet containing 0, 0.5, or 1% GTE and 0% GTE to lean mice (n = 12) for 6‐wk. Then, serum alanine aminotransferase (ALT) and hepatic AOX defenses were measured. Obese compared to lean controls had 7‐fold greater ALT (p < 0.05) and GTE at 0.5 or 1% decreased ALT by 19‐25%. Mn and CuZn superoxide dismutase (SOD) activities were 25‐29% lower in obese mice and GTE increased Mn‐ and CuZn‐SOD by 29‐42% and 26‐28%, respectively. Catalase (CAT) activity was 40% lower in obese mice and GTE at 0.5 or 1% increased it 26‐42%. Glutathione peroxidase (GPx) activity of obese mice was 30% lower than lean controls and GTE increased it 14‐15%. Glutathione S‐transferase activity was greater in obese mice and further increased by GTE at 1% only. Glutathione reductase activity was higher in obese mice and unaffected by GTE. ALT was inversely related (p < 0.05) to CAT (r = ‐0.395) and GPx (r = ‐0.562) suggesting that these enzymatic AOX activities protect against hepatic injury. Collectively, these data suggest that GTE, in part, restores those AOX defenses impaired by obesity and that GTE may protect against hepatic injury associated with NAFLD. Supported by a grant from the USDA‐NRI (2007‐02303) to RSB.