Proteomic analysis of the inhibitory effect of epigallocatechin gallate on lipid accumulation in human HepG2 cells
TL;DR: The proteomic analysis hypothesized that EGCG reduced cellular lipid accumulation in FFA-induced HepG2 cells through the activation of AMP-activated protein kinase (AMPK) resulting from the generation of reactive oxygen species (ROS).
Abstract: Background
(−)-Epigallocatechin-3-gallate (EGCG), the most abundant catechin found in green tea, effectively reduces body weight and tissue and blood lipid accumulation. To explore the mechanism by which EGCG inhibits cellular lipid accumulation in free fatty acid (FFA) induced HepG2 cell culture, we investigated the proteome change of FFA-induced HepG2 cells exposed to EGCG using two-dimensional gel electrophoresis and mass spectrometry.
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TL;DR: The objectives of this paper are to review and discuss the currently known targets, signaling pathways and roles of EGCG that interfere with NAFLD pathogenesis, then providing additional experimental evidence and the foundation for the further studies and clinical applications of E GCG in the prevention and treatment ofNAFLD.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a major health issue throughout the world. However, no validated treatments for NAFLD are currently available. In-depth studies have demonstrated the efficacy of (-)-epigallocatechin-3-gallate (EGCG), a main bioactive chemical extracted from green tea, in treating NAFLD. EGCG exhibits multi-pronged preventive and therapeutic activities, including promoting lipid and glucose metabolism, anti-lipid peroxidation and anti-inflammation activities, anti-fibrosis, and anti-NAFLD related tumor, thus contributing to the mitigation of NAFLD occurrence and progression. The objectives of this paper are to review and discuss the currently known targets, signaling pathways and roles of EGCG that interfere with NAFLD pathogenesis, then providing additional experimental evidence and the foundation for the further studies and clinical applications of EGCG in the prevention and treatment of NAFLD.
54 citations
TL;DR: Alkaloid and polyphenol are promising candidates for metabolic diseases to ameliorate lipid metabolism abnormalities to improve or even curing lipid metabolism-related diseases.
37 citations
TL;DR: The effects of ChrSd supplementation in a HF diet on weight gain, insulin resistance, and progression of hepatic steatosis in DIO mice were associated with modulation of hepatics genes related to oxidative stress, inflammation, ceramide synthesis, and lipid and cholesterol metabolism.
Abstract: To identify differentially expressed hepatic genes contributing to the improvement of high-fat (HF) diet-induced hepatic steatosis and insulin resistance following supplementation of partially defatted flavonoid-rich Chardonnay grape seed flour (ChrSd), diet-induced obese (DIO) mice were fed HF diets containing either ChrSd or microcrystalline cellulose (MCC, control) for 5 weeks. The 2-h insulin area under the curve was significantly lowered by ChrSd, indicating that ChrSd improved insulin sensitivity. ChrSd intake also significantly reduced body weight gain, liver and adipose tissue weight, hepatic lipid content, and plasma low-density lipoprotein (LDL)-cholesterol, despite a significant increase in food intake. Exon microarray analysis of hepatic gene expression revealed down-regulation of genes related to triglyceride and ceramide synthesis, immune response, oxidative stress, and inflammation and upregulation of genes related to fatty acid oxidation, cholesterol, and bile acid synthesis. In conclusion, the effects of ChrSd supplementation in a HF diet on weight gain, insulin resistance, and progression of hepatic steatosis in DIO mice were associated with modulation of hepatic genes related to oxidative stress, inflammation, ceramide synthesis, and lipid and cholesterol metabolism.
25 citations
TL;DR: It is demonstrated that the extract of S. reticulata has therapeutic effects on obesity and metabolic disorders by enhancing lipogenesis genes and suppressing lipolysis genes through the activation of AMPKα in adipocytes.
Abstract: Salacia reticulata Wight (S. reticulata) is a herbal medicine used for treatment of early diabetes in Ayurvedic medicine. In previous reports, the extract of S. reticulata showed preventive effects on obesity and various metabolic disorders and a suppressive effect on differentiation in premature adipocytes. The aim of this research was to elucidate the therapeutic efficacy of the extract of S. reticulata on obesity and various metabolic disorders in 12-week-old TSOD mice with obesity and metabolic disorders and in mature 3T3-L1 adipocytes. In TSOD mice, S. reticulata therapy produced a reduction in body weight and mesenteric fat accumulation, an improvement in abnormal glucose metabolism, and an increase in adiponectin level in plasma. In addition, the mRNA expressions of hormone-sensitive lipase (HSL) and adiponectin were increased in mesenteric fat. In in vitro experiments, S. reticulata therapy produced suppression of intracellular triacylglycerol accumulation and enhancement of glycerol release into the medium in mature 3T3-L1 cells. The mRNA expressions of lipogenesis factor (peroxisome proliferator-activated receptor γ, lipoprotein lipase, CD36, and fatty acid binding protein 4) were down-regulated, while the expressions of lipolysis factor (adipose tissue triacylglycerol lipase and HSL) and adiponectin were up-regulated. Moreover, the extract of S. reticulata enhanced the expression of total AMP-activated protein kinase α (AMPKα) and phosphorylated AMPKα in mature adipocytes. These findings demonstrate that the extract of S. reticulata has therapeutic effects on obesity and metabolic disorders by enhancing lipogenesis genes and suppressing lipolysis genes through the activation of AMPKα in adipocytes.
17 citations
TL;DR: The C. longa extract is suggested to have the anti-adipogenesis potential on inhibiting the synthesis of triglycerides and cholesterol and lipid droplet formation in HepG2 cell as anti-obesity parameters better than curcumin.
Abstract: Background: Adipocytes accumulate triacylglycerol when excessive food consumption. Adipocyte dysfunction plays an important role in the obesity development. People with a body weight 40 % heavier than the average body weight population at risk of death two times greater than the average body weight. The use of anti-obesity drugs have many side effects, so it is necessary to find the anti-obesity drug with low toxicity. This ex vivo study was conducted to determine the activity of C. longa L. extract in inhibiting triglycerides and cholesterol synthesis and lipid droplet formation on HepG2 cells compared to curcumin. Methods: Anti-obesity activity includes reduced formation of lipid droplet in HepG2 cells can be observed using oil red O staining method. The measurement of triglyceride level was performed according to Randox protocol using Randox TR 210 assay kit. Lipolytic activity by measuring cholesterol levels was performed based on Randox CH 200 kits. Results: This study suggested that the extract of C. longa L. and curcumin have potential anti-obesity compounds. C. longa L. extract have higher activity in inhibiting triglycerides and cholesterol synthesis compared to curcumin with inhibition activities 70.43% and 66.38% respectively in the highest concentration. Conclusion: The C. longa extract posses the anti-adipogenesis potential on inhibiting the synthesis of triglycerides and cholesterol and lipid droplet formation in HepG2 cell as anti-obesity parameters better than curcumin.
11 citations
References
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TL;DR: Evidence that this protein has enzymatic activity similar to that of lysosomal cathepsin A is provided and indicates that the catalytic activity and protective function of the protective protein are distinct.
159 citations
TL;DR: GA significantly reduced FFA/HFD‐induced hepatic lipotoxicity by stabilizing the integrity of lysosomes and mitochondria and inhibiting cathepsin B expression and enzyme activity, and reduce FFA‐induced oxidative stress.
145 citations
"Proteomic analysis of the inhibitor..." refers methods in this paper
...To induce fat-overloading, HepG2 cells were exposed to 1 mM of FFA mixture (OA / PA, 2:1) mixed with 1% FFA-free bovine serum albumin [17,28,62]....
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09 Mar 2012
TL;DR: This review summarizes several lines of evidence to indicate the health-promoting properties of green tea mainly based on the authors' own experimental findings.
Abstract: Green tea is manufactured from the leaves of the plant Camellia sinensis Theaceae and has been regarded to possess anti-cancer, anti-obesity, anti-atherosclerotic, anti-diabetic, anti-bacterial, and anti-viral effects. Many of the beneficial effects of green tea are related to the activities of (-)-epigallocatechin gallate (EGCG), a major component of green tea catechins. For about 20 years, we have engaged in studies to reveal the biological activities and action mechanisms of green tea and EGCG. This review summarizes several lines of evidence to indicate the health-promoting properties of green tea mainly based on our own experimental findings.
137 citations
"Proteomic analysis of the inhibitor..." refers background in this paper
...Research indicates that green tea is beneficial to health and many components of tea have specific health-promoting effects [2,3]....
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TL;DR: It is suggested that teapolyphenols suppress FAS expression by downregulating EGF receptor/PI3K/Akt/Sp-1 signal transduction pathway, and tea and tea polyphenols might induce hypolipidemic and antiproliferative effects by suppressing FAS.
Abstract: Tea is a heavily consumed beverage world wide because of its unique aroma, less cost and broad availability. Fatty acid synthase (FAS) is a key enzyme in lipogenesis. FAS is overexpressed in the malignant human breast carcinoma MCF-7 cells and its expression is further enhanced by the epidermal growth factor (EGF). The EGF-induced expression of FAS was inhibited by green and black tea extracts. The expression of FAS was also suppressed by the tea polyphenol (-)-epigallocatechin 3-gallate (EGCG), theaflavin (TF-1), TF-2 and theaflavin 3,3'-digallate(TF-3) at both protein and mRNA levels that may lead to the inhibition of cell lipogenesis and proliferation. Both EGCG and TF-3 inhibit the activation of Akt and block the binding of Sp-1 to its target site. Furthermore, the EGF-induced biosyntheses of lipids and cell proliferation were significantly suppressed by EGCG and TF-3. These findings suggest that tea polyphenols suppress FAS expression by downregulating EGF receptor/PI3K/Akt/Sp-1 signal transduction pathway, and tea and tea polyphenols might induce hypolipidemic and antiproliferative effects by suppressing FAS.
120 citations
"Proteomic analysis of the inhibitor..." refers background in this paper
...Moreover, EGCG treatment down-regulated several genes related to fatty acid synthesis and storage in the liver and white adipose tissue, including acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PDH), glycerol-3 -phosphate dehydrogenase (G3PDH), and stearoyl-CoA desaturase-1 (SCD1) [12-15]....
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TL;DR: The results indicate that 1-cysPrx can function in the intact cell as an antioxidant enzyme to reduce the accumulation of phospholipid hydroperoxides and prevent apoptotic cell death.
118 citations
"Proteomic analysis of the inhibitor..." refers background in this paper
...Prdx6 is the sixth mammalian member of the peroxiredoxin family, which has an important role in antioxidant defense [25,26]....
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