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Journal ArticleDOI

Proteomic analysis of the inhibitory effect of epigallocatechin gallate on lipid accumulation in human HepG2 cells

18 Jul 2013-Proteome Science (BioMed Central)-Vol. 11, Iss: 1, pp 32-32
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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Citations
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Journal ArticleDOI
Cheng Chen1, Qian Liu1, Lin Liu1, Yi-Yang Hu1, Qin Feng1 
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

Journal ArticleDOI
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

Journal ArticleDOI
15 Dec 2016-PLOS ONE
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

Journal ArticleDOI
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

Journal ArticleDOI
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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Journal ArticleDOI
TL;DR: Under this heightened scrutiny, the succinate dehydrogenase complex has proven to be a fascinating machine, whose regulation and assembly requires additional factors that are beginning to be discovered.

332 citations


"Proteomic analysis of the inhibitor..." refers background in this paper

  • ...Succinate dehydrogenase (SDH or ubiquinone) is an enzyme that controls the transcription of metabolism-related genes in mitochondria and promotes metabolism of glucose and lipids [32,33]....

    [...]

Journal ArticleDOI
TL;DR: The mechanistic results of this review may possibly be utilized in the treatment of obesity, diabetes, and other related diseases using tea- and EGCG-based folk medicines.
Abstract: Tea has been found to possess widespread biological functions based on a variety of laboratory data. The effects of tea on obesity and diabetes have received increasing attention. This paper reviews the evidence for the connections among tea catechins, and obesity and diabetes. Tea catechins, especially (-)-epigallocatechin gallate (EGCG), appear to have antiobesity and antidiabetic effects. While few epidemiological and clinical studies show the health benefits of EGCG on obesity and diabetes, the mechanisms of its actions are emerging based on the various laboratory data. These mechanisms may be related to certain pathways, such as through the modulations of energy balance, endocrine systems, food intake, lipid and carbohydrate metabolism, the redox status, and activities of different types of cells (i. e., fat, liver, muscle, and beta-pancreatic cells). Because the EGCG receptor, the so-called 67-kDa laminin receptor (LR), has been discovered with colocalization of other types of LR and cytoskeleton in both cancer cells and normal cells, this may explain that EGCG possesses numerous actions. The mechanistic results of this review may possibly be utilized in the treatment of obesity, diabetes, and other related diseases using tea- and EGCG-based folk medicines.

320 citations


"Proteomic analysis of the inhibitor..." refers background or methods in this paper

  • ...Studies have suggested that (−)-epigallocatechin-3-gallate (EGCG), the most abundant catechin found in green tea, could effectively reduce body weight and tissue and blood fat accumulation [4,5]....

    [...]

  • ...The cells were lysed in lysis buffer (7 M urea, 2 M thiourea, 4% [w/v] CHAPS, 65 mM DTT, 2% [v/v] Bio-Lyte pH [3-10], 2% protease inhibitor cocktail), mixed by vortexing, kept in an ice bath for 2 h, then sonicated in an ice bath....

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Journal ArticleDOI
TL;DR: Gene silencing of 14-3-3σ by CpG methylation has been found in many human cancer types, which suggests that therapy-targeting 14- 3- 3σ may be beneficial for future cancer treatment.
Abstract: 14-3-3 is a highly conserved acidic protein family, composed of seven isoforms in mammals. 14-3-3 protein can interact with over 200 target proteins by phosphoserine-dependent and phosphoserine-independent manners. Little is known about the consequences of these interactions, and thus are the subjects of ongoing studies. 14-3-3 controls cell cycle, cell growth, differentiation, survival, apoptosis, migration and spreading. Recent studies have revealed new mechanisms and new functions of 14-3-3, giving us more insights on this fascinating and complex family of proteins. Of all the seven isoforms, 14-3-3sigma seems to be directly involved in human cancer. 14-3-3sigma itself is subject to regulation by p53 upon DNA damage and by epigenetic deregulation. Gene silencing of 14-3-3sigma by CpG methylation has been found in many human cancer types. This suggests that therapy-targeting 14-3-3sigma may be beneficial for future cancer treatment.

300 citations

Journal ArticleDOI
TL;DR: It is shown that hypoxia activates AMPK through LKB1 without an increase in the AMP/ATP ratio, and genetic evidence is provided that ROS generated within the mitochondrial electron transport chain and not oxidative phosphorylation is required for hypoxic activation of AMPK.

288 citations


"Proteomic analysis of the inhibitor..." refers background in this paper

  • ...Several studies reported that an increase in reactive oxygen species (ROS) could lead to AMPK activation [27,28]....

    [...]

Journal ArticleDOI
TL;DR: The nature of the substrates hydrolyzed by PAF acetylhydrolases points at key roles for these activities in physiology and pathology, and it has provided important clues into what is currently thought to be the main function of these enzymes, which is to act as scavengers of bioactive phospholipids.

271 citations


"Proteomic analysis of the inhibitor..." refers background in this paper

  • ...Plateletactivating factor acetylhydrolase (PAFAH), a unique member of the phospholipase A2 superfamily, is characterized by its ability to specifically hydrolyze plateletactivating factor (PAF) and glycerophospholipids [40]....

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