Progress 01/01/08 to 12/31/11
Outputs
OUTPUTS: The underlying objective of this project was to examine the hepatoprotective activities of green tea extract (GTE) in animal models of enhanced oxidative stress and inflammation. Specifically, we used obese models of nonalcoholic steatohepatitis (NASH), a disorder characterized by extensive liver injury due to oxidative stress and inflammatory responses that promote fatty infiltrates to the liver. Major outputs of this project include conducting controlled dietary intervention trials in genetically obese and diet-induced obese (DIO) rodent models of NASH. In the first study, we examined the extent to which the hypolipidemic and antioxidant activities of GTE would attenuate pro-inflammatory and lipogenic responses leading to liver injury and NASH in obese (ob/ob) mice. For this study, obese (ob/ob) mice and their lean littermate controls were fed GTE at 0%, 0.5% or 1% (w/w) for 6 weeks. Then, hepatic steatosis and injury, oxidative stress, and inflammatory markers were measured. In our second study, we utilized specimens from the above study to investigate whether the anti-inflammatory properties of GTE would protect against NASH in obese (ob/ob) mice by suppressing oxidative and nitrative damage mediated by pro-inflammatory enzymes. To complement these studies, and determine whether GTE protects against NASH independent of leptin status, we conducted a dietary intervention in a DIO model to determine the antioxidant and anti-inflammatory activities of GTE that protect against NASH. For this study, Wistar rats were fed a low-fat diet or high-fat diet containing GTE at 0, 1, or 2% for 8 wk and then parameters of NASH and nuclear factor kappa B (NFkB)-dependent inflammatory responses were evaluated at liver and adipose. In a separate study using the specimens from the DIO model, we investigated whether the anti-inflammatory and hypolipidemic activities of GTE would suppress COX-2-mediated prostaglandin accumulation at the liver. Collectively, these works have provided seminal knowledge of the hypolipidemic, anti-oxidant, and anti-inflammatory activities of GTE in models systems recapitulating humans with NASH. PARTICIPANTS: Richard Bruno, PhD, RD. Dr. Bruno (PI; University of Connecticut) was responsible for the overall direction and progress of the project and the individuals engaged on the project. Ji-Young Lee, PhD. Dr. Lee (University of Nebraska) was contracted to the project. She contributed to its success by examining expression levels of inflammatory-related genes from liver and adipose. Hea Jin Park, PhD. Dr. Park (Post-Doc; University of Connecticut) was responsible for performing experiments, generating data, and assembling reports associated with the project. Min-Yu Chung, MS. Ms. Chung (Graduate Research Assistant; University of Connecticut) was responsible for animal care, performing experiments, generating data, and assembling reports associated with the project. Dana A DiNatale, BS. Ms. DiNatale was a Graduate Research Assistant under the supervision of the PI who is responsible for conducting experiments to evaluate the regulatory actions of green tea extract on hepatic enzymatic antioxidant defenses. TARGET AUDIENCES: This scope of this project is of considerable public and scientific interest because the incidence of NAFLD has paralleled the ongoing obesity epidemic and it is estimated that 70 million Americans are afflicted with this tragic and asymptomatic disease. Thus, the intended target audience of this work is obese individuals and those at risk for becoming obese. Efforts have been taken to initiate an education program about the protective effects of green tea by presenting oral and poster presentations at scientific meetings (Experimental Biology, Society of Toxicology, and Institute of Food Technologists). In addition, the PI has shared the scientific findings and recommendations of the project by serving as an invited speaker at academic institutes and on a call-in radio show sponsored by an industry group. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
Our studies have provided substantial information that defines the mechanisms by which GTE protects against oxidative and inflammatory insults leading to NASH. Studies in ob/ob mice show that GTE lowered hepatic lipids and alanine aminotransferase (ALT). GTE-mediated decreases in liver steatosis were accompanied by lower expression of adipose lipogenic genes and lower serum nonesterified fatty acid concentrations. Steatotic livers from ob/ob mice had higher tumor necrosis factor-a (TNFa), whereas GTE decreased hepatic and adipose TNFa expression. Hepatic glutathione, malondialdehyde and enzymatic antioxidant defenses were also increased in response to GTE. Separate studies in ob/ob mice show that GTE normalizes hepatic hydroxynonenal and nitro-tyrosine (N-Tyr) to those of lean controls. Decreases in oxidative and nitrative damage by GTE were associated with lower hepatic NADPH oxidase activity and expression of myeloperoxidase and inducible nitric oxide synthase. Correlations between NADPH oxidase and hydroxynonenal as well as nitric oxide metabolites and N-Tyr support that GTE reduces lipid peroxidation and protein nitration by decreasing reactive oxygen/nitrogen species generation. Thus, studies in ob/ob mice demonstrate that GTE attenuates NASH by decreasing the flux of fatty acids from adipose to liver and inhibiting lipid peroxidation as well as restoring antioxidant defenses and inflammatory responses. Studies in the DIO model show that GTE attenuates hepatic steatosis and injury otherwise induced by high-fat feeding. High-fat feeding decreased liver and epididymal adipose glutathione and increased the expression of TNFa and monocyte chemoattractant protein-1 and NFκB binding activity. GTE increased glutathione and decreased inflammatory cytokine expression at liver and adipose. Tissue NFkB binding activities were also lower in association with lower phosphorylation of inhibitor of NFκB. Separate studies in the DIO model show that GTE attenuates liver steatosis in association with greater expression of carnitine palmitoyltransferase. GTE also reduces hepatic malondialdehyde without affecting mRNA expression of CYP2E1 that were otherwise increased by high-fat feeding. Hepatic COX-2 expression and activity were greater in high-fat controls and decreased in response to GTE. GTE normalized prostaglandin E2 (PGE2) accumulation to that of low-fat controls. GTE also reduced hepatic total arachidonic acid, but without affecting cytosolic phospholipase2 activity or arachidonic acid levels in phospholipid or nonesterified fatty acid lipid pools. Thus, these studies in the DIO model suggest that GTE-mediated improvements in glutathione status are associated with lower inflammatory responses mediated by NFκB, thereby protecting against NASH. Likewise, GTE reduces hepatic lipid peroxidation and PGE2 accumulation by inhibiting COX-2 activity independent of arachidonic acid availability. Collectively, the findings of this project better define the antioxidant and anti-inflammatory activities of GTE that protect against liver steatosis, oxidative damage, and NFkB-dependent inflammatory responses during NASH.
Publications
- Chung MY, Park HJ, Manautou JE, Koo SI, Bruno RS. Green tea extract protects against nonalcoholic steatohepatitis in ob/ob mice by decreasing oxidative and nitrative stress responses induced by proinflammatory enzymes. J Nutr Biochem. 2011, E-pub May 2.
- Chung MY, Yeung SF, Park HJ, Volek JS, Bruno RS. Dietary alpha- and gamma-tocopherol supplementation attenuates lipopolysaccharide-induced oxidative stress and inflammatory-related responses in an obese mouse model of nonalcoholic steatohepatitis. J Nutr Biochem. 2010;21:1200-6.
- Hsu A, Bruno RS, Lohr CV, Taylor AW, Dashwood RH, Bray TM, Ho E. Dietary soy and tea mitigate chronic inflammation and prostate cancer via NFkappaB pathway in the Noble rat model. J Nutr Biochem. 2011;22:502-10.
- Masterjohn C, Bruno RS. Therapeutic potential of green tea in nonalcoholic fatty liver disease. Nutr Rev. 2012;70:41-56.
- Park HJ, Lee JY, Chung MY, Park YK, Bower AM, Koo SI, Giardina C, Bruno RS. Green tea extract suppresses NFkappaB activation and inflammatory responses in diet-induced obese rats with nonalcoholic steatohepatitis. J Nutr. 2012;142:57-63.
- Wong CP, Nguyen LP, Noh SK, Bray TM, Bruno RS, Ho E. Induction of regulatory T cells by green tea polyphenol EGCG. Immunol Lett. 2011;139:7-13.
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Progress 01/01/10 to 12/31/10
Outputs
OUTPUTS: Nonalcoholic steatohepatitis (NASH) is characterized by oxidative stress and inflammatory responses that exacerbate liver injury. During the past reporting period, our primary output was to examine whether the antioxidant and anti-inflammatory activities of green tea extract (GTE) would protect against NASH in a model of diet-induced obesity. We fed adult Wistar rats a low-fat (LF) or a high-fat (HF) diet containing 0, 1, or 2% GTE (n = 15-16/group) for 8 wk. HF feeding increased (P<0.05) serum alanine (ALT) and aspartate (AST) aminotransferases and hepatic lipid accumulation. GTE reduced ALT and AST, and normalized hepatic lipid concentrations to those of LF controls. HF feeding increased mRNA expression and protein concentrations of hepatic and epididymal adipose tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1). GTE decreased protein concentrations of TNF-α and MCP-1 and normalized their mRNA expression of levels at both tissues. GTE improved hepatic and epididymal glutathione concentrations that were otherwise decreased by HF-feeding. HF-feeding increased hepatic and epididymal adipose NFκB binding activities and GTE normalized this effect at both tissues to levels seen in LF controls. GTE also inhibited IκB phosphorylation at liver and epididymal adipose. NFκB binding activities in liver and epididymal adipose (P<0.05; r = 0.616 and 0.461, respectively) were correlated with ALT, and hepatic NFκB binding activity was inversely related to liver glutathione (r = -0.350). These results suggest that GTE-mediated improvements in glutathione status protect against NASH by inhibiting hepatic and adipose inflammatory responses under the transcriptional regulation of NFκB. Additional study is underway to examine whether GTE suppresses other pro-inflammatory proteins under the transcriptional control of NFkB. PARTICIPANTS: Richard Bruno, PhD, RD. Dr. Bruno (PI; University of Connecticut) was responsible for the overall direction and progress of the project and the individuals engaged on the project. Ji-Young Lee, PhD. Dr. Lee (co-PI; University of Nebraska) was contracted to the project. She contributed to its success by examining expression levels of inflammatory-related genes from liver and adipose. Hea Jin Park, PhD. Dr. Park (Post-Doc; University of Connecticut) was responsible for performing experiments, generating data, and assembling reports associated with the project. Min-Yu Chung, MS. Ms. Chung (Graduate Student; University of Connecticut) was responsible for animal care, performing experiments, generating data, and assembling reports associated with the project. TARGET AUDIENCES: This scope of this project is of considerable public and scientific interest because the incidence of NAFLD has paralleled the ongoing obesity epidemic and it is estimated that >70 million adults are afflicted with this tragic and asymptomatic disease. Thus, the intended target audience of this work is obese individuals and those with a propensity for becoming obese. Continued efforts are underway to educate the scientific community regarding the protective effects of green tea by submitting abstracts for presentation at national scientific meetings (i.e. Experimental Biology). In addition, the PI has shared the scientific findings and recommendations of the project by serving as a guest speaker at various academic institutions. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
We have provided the first evidence that GTE regulates NFkB activation and its downstream pro-inflammatory responses in a model of diet-induced obesity and NASH. These findings, in part, provide a mechanism to support epidemiological knowledge that green tea consumption decreases the risk for liver disease and cardiovascular disease. Accordingly, these studies are expected to support future trials in humans aimed at validating the hypolipidemic and anti-inflammatory activities of GTE in humans having or vulnerable to NAFLD.
Publications
- Montrose DC, Horelik NA, Madigan JP, Stoner GD, Wang LS, Bruno RS, Park HJ, Giardina C, Rosenberg DW. Anti-inflammatory effects of freeze-dried black raspberry powder in ulcerative colitis. Carcinogenesis. 2011;32(3):343-50. Epub 2010 Nov 23.
- Park HJ, Dinatale DA, Chung MY, Park YK, Lee JY, Koo SI, O'Connor M, Manautou JE, Bruno RS. Green tea extract attenuates hepatic steatosis by decreasing adipose lipogenesis and enhancing hepatic antioxidant defenses in ob/ob mice. J Nutr Biochem. 2011;22(4):393-400. Epub 2010 Jul 23
- HJ Park and RS Bruno. Hepatoprotective Activities Of Green Tea In Nonalcoholic Fatty Liver Disease. AgroFOOD Industry High-tech. 2010;21(1): 37-40.
- Park HJ, Mah E, Bruno RS. Validation of high-performance liquid chromatography-boron-doped diamond detection for assessing hepatic glutathione redox status. Anal Biochem. 2010;407(2):151-9. Epub 2010 Aug 10.
- Park HJ, Dinatale DA, Chung MY, Park YK, Lee JY, Koo SI, O'Connor M, Manautou JE, Bruno RS. Green tea extract attenuates hepatic steatosis by decreasing adipose lipogenesis and enhancing hepatic antioxidant defenses in ob/ob mice. J Nutr Biochem. 2011;22(4):393-400. Epub 2010 Jul 23.
- HJ Park, M-Y Chung, SI Koo, RS Bruno. Green tea extract attenuates adipose inflammation by restoring glutathione redox status in high fat diet-induced nonalcoholic fatty liver disease. FASEB J. 2010; 24:722.15.
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Progress 01/01/09 to 12/31/09
Outputs
OUTPUTS: There are two primary outputs for this reporting period: Output 1. To define the anti-inflammatory and antioxidant activities of green tea extract, we conducted a study in rats. We fed 16-wk old Wister rats (n = 63) a low-fat diet (LF, 10% of kcal) containing 0% GTE or high-fat diet (HF, 60% of kcal) containing 0, 1, or 2% GTE for 8-wk. HF-fed rats compared to LF controls had 2-fold greater (p<0.05) serum ALT and GTE at 1-2% decreased it by 38-39%. Hepatic and adipose monocyte chemoattractant protein (MCP-1) was 1.5- and 1.3-fold higher in HF-fed rats and GTE reduced them up to 64% and 25%. Dietary fat levels did not affect hepatic or adipose TNF-α, but GTE at 2% reduced them by 29-33%. HF-fed rats had 27% and 32% lower reduced glutathione (GSH) in liver and adipose, respectively, suggesting that HF feeding induced oxidative stress. GTE at 2% increased adipose and liver GSH by 19% and 43%. Serum ALT was correlated (p<0.05) to hepatic TNF-α and MCP-1 and adipose MCP-1. In liver, MCP-1 was inversely related to GSH, suggesting that oxidative stress was associated with hepatic inflammation. In adipose, MCP-1 was inversely related to the proportion of oxidized glutathione (%GSSG), suggesting that an oxidized thiol state in adipose decreases inflammation. These data suggest that GTE attenuates hepatic injury by reducing inflammation in liver and adipose and that glutathione redox status may play a critical role on anti-inflammatory effect of GTE in liver and adipose. Additional study is underway to define the role of glutathione on inflammation in GTE supplementation. Output 2. Glutathione redox status is commonly used oxidative stress biomarker. Thus, we aimed to validate an HPLC-ECD approach using boron-doped diamond (BDD), a novel electrode material having excellent electrochemical stability. Mice (n=4/group) were injected with lipopolysaccharide (LPS, 0 or 4 mg/kg) and sacrificed 24 h later. Liver homogenates prepared in parallel were analyzed by HPLC-BDD and -UV. HPLC-BDD responses for reduced (GSH) and oxidized (GSSG) glutathione were linear over >4 orders of magnitude at 1475 mV, the optimal oxidation potential. Within- and between-day coefficient of variations of GSH, GSSG, and the GSH/GSSG ratio were <8% and electrochemical responses were stable up to 48 h of continuous system use. Using HPLC-BDD or -UV, decreases (P<0.05) in hepatic GSH and the GSH/GSSG ratio were observed following LPS administration. However, LPS-triggered increases in GSSG were only observed using HPLC-BDD. Moreover, GSSG determined by HPLC-BDD and -UV was not correlated, and optically-generated values were ~4.5-times greater on average, supporting greater selectivity of HPLC-BDD. Collectively, our findings support HPLC-BDD as a relatively simple, sensitive, and validated approach for evaluating hepatic glutathione redox status. PARTICIPANTS: Richard Bruno, PhD, RD. Dr. Bruno (PI; University of Connecticut) was responsible for the overall direction and progress of the project and the individuals engaged on the project. Ji-Young Lee, PhD. Dr. Lee (co-PI; University of Nebraska) was contracted to the project. She contributed to its success by examining expression levels of inflammatory-related genes from liver and adipose. Hea Jin Park, PhD. Dr. Park (Post-Doc; University of Connecticut) was responsible for performing experiments, generating data, and assembling reports associated with the project. Min-Yu Chung, MS. Ms. Chung (Graduate Student; University of Connecticut) was responsible for animal care, performing experiments, generating data, and assembling reports associated with the project. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
There are two major outcomes of these projects. First, we have provided the first evidence of a validated method for the determination of tissue glutathione redox using HPLC-BDD. This novel approach is more economical, reliable, and has greater throughput for sample analysis than commonly used HPLC-UV techniques. Second, we have established that GTE exerts significant anti-inflammatory actions that decrease the vulnerability of the liver to hepatic injury. These findings, in part, support the existing epidemiological knowledge whereby green tea consumption decreases the risk for liver disease and cardiovascular disease. Of particular importance, the latter outcome is supportive for future trials in humans aimed at validating antioxidant and anti-inflammatory activities in humans having or vulnerable to NAFLD.
Publications
- Iwaniec, U.T., Turner, R.T., Koo, S.I., Kaur, R., Ho, E., Wong, C.P., Bruno, R.S. 2009. Consumption of Green Tea Extract Results in Osteopenia in Growing Mice. J. Nutr. 139(10):1914-9
- Chung, M-Y., Yeung, S.F. DiNatale, D.A., Volek, J.S., Bruno, R.S. 2010. Dietary α- and γ-Tocopherol Protect Against LPS-triggered hepatic injury in spontaneously obese mice. J. Nutr. Biochem. In press
- Park, H.J., Davis, S.R., Liang, H-Y., Rosenberg, D.W., Bruno, R.S. 2010. Chlorogenic acid differentially alters hepatic and small intestinal thiol redox status without protecting against azoxymethane-induced colon carcinogenesis in mice. Nutr. Cancer In press
- Park, H.J., Bruno, R.S. 2010. Hepatoprotective Activities Of Green Tea In Nonalcoholic Fatty Liver Disease. AgroFOOD Industry High-tech. In press
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Progress 01/01/08 to 12/31/08
Outputs
OUTPUTS: The tea plant (Camellia sinensis) is used to produce green tea, black tea, and oolong tea. Green tea is produced by immediately withering and steaming the leaves upon harvest which preserves the polyphenolic catechins, the bioactive compounds of green tea thought to have antioxidant activities. Epidemiological data suggested that the consumption of green tea was inversely related to the incidence of cardiovascular disease and all cause mortality and green tea or its catechins were suggested to regulate body weight, increase lipid metabolism, and decrease lipid absorption. Thus, the scope of this USDA project is to define the bioactive properties of green tea in regulating the underlying events that contribute to the development of obesity-triggered hepatic steatosis, a silent and tragic disease caused by obesity, insulin resistance, and excess hepatic lipid accumulation that can lead to liver injury or failure. The outputs for this project include: 1. Conducting a study to evaluate the hepatic lipid lowering and antioxidant bioactivities of green tea extract in genetically obese mice prone to the development of hepatic steatosis. 2. Analyzing and preparing data for presentation at national scientific meetings. 3. Participating as an invited guest speaker on Clinical Rounds radio show (Designs for Health, Inc) to discuss green tea for fatty liver disease. PARTICIPANTS: Richard S Bruno, PhD, RD. Dr. Bruno (Principal Investigator) is responsible for the overall management and direction of the project. He supervises the progress of each individual engaged on the project and provides technical expertise as appropriate. Hea Jin Park, PhD. Dr. Park is a post-doc under the supervision of the PI who is enlisted on the project at 100% effort. She is responsible for conducting experiments to evaluate the protective actions of green tea extract on hepatic lipid accumulation during the development of hepatic steatosis. She is also responsible for preparing reports of experimental findings and for co-authoring publications. Dana A DiNatale, BS. Ms. DiNatale is a graduate student under the supervision of the PI who is responsible for conducting experiments to evaluate the regulatory actions of green tea extract on hepatic enzymatic antioxidant defenses. Min-Yu Chung, MS. Ms Chung is a doctoral student under the supervision of the PI who is enlisted on the project to evaluate the anti-inflammatory activities of green tea extract on obese mice with hepatic steatosis. Ji-Young Lee, PhD. Dr. Lee (co-I) is a molecular nutritionist who is performing experiments to determine the extent to which green tea extract regulates the expression and concentrations of proteins involved in lipogenesis, inflammation and antioxidant defense. Sung I Koo, PhD. Dr. Koo (co-I) has extensive expertise in lipid metabolism. He is responsible for assisting with the interpretation of experiments aimed at determining the hypolipidemic activities of green tea extract during the development of hepatic steatosis. TARGET AUDIENCES: This scope of this project is of considerable public and scientific interest because the incidence of NAFLD has paralleled the ongoing obesity epidemic and it is estimated that ~40 million adults are afflicted with this tragic and silent disease. Thus, the intended target audience of this work is obese individuals and those with a propensity for becoming obese. Efforts have been taken to initiate an education program about the protective effects of green tea by submitting abstracts for poster presentations at national scientific meetings (Experimental Biology and Institute of Food Technologists). In addition, the PI has shared the scientific findings and recommendations of the project by serving as a guest speaker on a call-in radio show sponsored by the nutraceuticals company Designs for Health, Inc. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
We previously demonstrated that GTE protects against hepatic steatosis and hepatic injury in obese mice. Thus, we conducted a dietary intervention study to determine whether GTE would also mitigate hepatic oxidative stress responses simultaneously with improvements in hepatic steatosis. We fed 5-wk old obese (ob/ob) mice (n=38) diets containing 0, 0.5 or 1% GTE or lean controls 0% GTE (n=12) for 6-wk. Subsequently, hepatic lipids and injury, hepatic enzymatic antioxidant defenses, and serum TNF-a were evaluated. Serum alanine aminotransferase (ALT) was 7.3-times higher (p<0.05) in obese controls and 19-25% lower in obese mice fed GTE suggesting that GTE protects against obesity-induced hepatic injury. Hepatic total lipid (TL) was 2.3-times higher in obese mice and was 13% lower in obese mice fed 1% GTE demonstrating that GTE, at least in part, protects against hepatic steatosis. Consistent effects were observed for hepatic triglyceride (TG) and cholesterol (CHOL). Obese mice, compared to lean mice, had 16% lower hepatic total glutathione (tGSH) and 40% higher malondialdehyde (MDA) which were normalized by GTE to levels observed in lean mice. Hepatic Mn- and Cu/Zn-superoxide dismutase (SOD) activities were 25-29% lower in obese mice and GTE increased these by 29-42% and 26-28%, respectively. Hepatic catalase (CAT) and glutathione peroxidase (GPx) activities were 40% and 30% lower, respectively, in obese mice and GTE increased these by 26-42% and 14-15%. Obese mice had higher hepatic glutathione S-transferase (GST) and glutathione reductase (GR) activities and GST, but not GR, increased further in mice fed 1% GTE. Altered lipogenic gene expression may be involved in the hepatic lipid lowering effect of GTE. Serum TNF-α concentration was higher in obese controls compared to lean littermates and was reduced significantly by GTE at 1%. ALT was correlated to tGSH (r = -0.339), MDA (r = 0.358), CAT (r = -0.395), GPx (r = -0.562), TL (r = 0.895), TG (r = 0.777) and CHOL (r = 0.634). Collectively, these data suggest that GTE decreases obesity-triggered hepatic injury and hepatic oxidative stress responses associated with hepatic steatosis by restoring antioxidant defenses and inhibiting hepatic lipid accumulation.
Publications
- Chung, M.Y., O'Connor, M., Park, H.J., DiNatale, D., Koo, S.I., Manautou, J., Bruno, R.S. 2009. GTE reduces hepatic injury by inhibiting lipid accumulation and peroxidation in steatotic livers of obese mice. Federation of American Societies for Experimental Biology; New Orleans, LA. FASEB J. Abstract
- DiNatale, D.A., Park, H.J., Chung, M-Y., Koo, S.I., Bruno, R.S. 2009. Green tea extract (GTE) protects against nonalcoholic fatty liver disease (NAFLD) in obese mice by decreasing liver injury and improving enzymatic antioxidant defenses. Federation of American Societies for Experimental Biology; New Orleans, LA. FASEB J. Abstract
- Park, H.J., DiNatale, D.A., Chung, M-Y., Koo, S.I., Park, Y-K., Lee, J-Y., Bruno, R.S. 2009. Green tea extract (GTE) attenuates hepatic injury by reducing oxidative stress and lipid accumulation in ob/ob mice. Federation of American Societies for Experimental Biology; New Orleans, LA. FASEB J. Abstract
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