Yangha Kim

Green Tea (–)-Epigallocatechin-3-Gallate Reduces Body Weight with Regulation of Multiple Genes Expression in Adipose Tissue of Diet-Induced Obese Mice

Aims: The aim of this study was to investigate the antiobesity effect of (–)-epigallocatechin-3-gallate (EGCG) in diet-induced obese mice. Methods: Male C57BL/6J mice were fed on a high-fat diet for 8 weeks to induce obesity. Subsequently they were divided into 3 groups and were maintained on a high-fat control diet or high-fat diets supplemented with 0.2 or 0.5% EGCG (w/w) for a further 8 weeks. Changes in the expression of genes related to lipid metabolism and fatty acid oxidation were analyzed in white adipose tissue, together with biometric and blood parameters. Results: Experimental diets supplemented with EGCG resulted in reduction of body weight and mass of various adipose tissues in a dose-dependent manner. EGCG diet also considerably lowered the levels of plasma triglyceride and liver lipid. In the epididymal white adipose tissue of EGCG diet-fed mice, the mRNA levels of adipogenic genes such as peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT enhancer-binding protein-α (C/EBP-α), regulatory element-binding protein-1c (SREBP-1c), adipocyte fatty acid-binding protein (aP2), lipoprotein lipase (LPL) and fatty acid synthase (FAS) were significantly decreased. However, the mRNA levels of carnitine palmitoyl transferase-1 (CPT-1) and uncoupling protein 2 (UCP2), as well as lipolytic genes such as hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL), were significantly increased. Conclusion: These results suggest that green tea EGCG effectively reduces adipose tissue mass and ameliorates plasma lipid profiles in high-fat diet-induced obese mice. These effects might be at least partially mediated via regulation of the expression of multiple genes involved in adipogenesis, lipolysis, β-oxidation and thermogenesis in white adipose tissue.

Inhibitory effects of green tea catechin on the lipid accumulation in 3T3-L1 adipocytes.

The aim of the present study was to evaluate the effects of green tea (‐)‐epigallocatechin‐3‐gallate (EGCG) on the depletion of accumulated fat in differentiated 3T3‐L1 adipocytes. Intracellular lipid accumulation was decreased significantly after 24 h of incubation with 10 µm EGCG, while the viability of adipocytes was reported to be unaffected. Under the same experimental conditions, the amount of glycerol released from cells into the medium was increased by 10 µm EGCG. The level of mRNA in the 3T3‐L1 adipocytes was analysed by quantitative real‐time RT‐PCR. EGCG notably increased the mRNA level of hormone sensitive lipase (HSL), which catalyses the rate‐limiting stage in hydrolysis of stored triacylglycerol to monoacylglycerol and free fatty acids. In conclusion, the experiment produced results which showed that green tea EGCG effectively depleted fat accumulation via the stimulation of lipolysis and increased HSL gene expression in 3T3‐L1 adipocytes. These results may relate to the mechanism by which EGCG modulates lipolysis in adipocytes. Copyright

Hypocholesterolemic effects of curcumin via up-regulation of cholesterol 7a-hydroxylase in rats fed a high fat diet

There is an increasing interest in curcumin (Curcuma longa L.) as a cardiovascular disease (CVD) protective agent via decreased blood total cholesterol and low-density lipoprotein-cholesterol (LDL-cholesterol) level. The aim of this study was to investigate further the potential mechanism in the hypocholesterolemic effect of curcumin by measuring cholesterol 7a-hydroxylase (CYP7A1), a rate limiting enzyme in the biosynthesis of bile acid from cholesterol, at the mRNA level. Male Sprague-Dawley rats were fed a 45% high fat diet or same diet supplemented with curcumin (0.1% wt/wt) for 8 weeks. The curcumin diet significantly decreased serum triglyceride (TG) by 27%, total cholesterol (TC) by 33.8%, and LDL-cholesterol by 56%, respectively as compared to control group. The curcumin-supplemented diet also significantly lowered the atherogenic index (AI) by 48% as compared to control group. Hepatic TG level was significantly reduced by 41% in rats fed with curcumin-supplemented diet in comparison with control group (P < 0.05). Conversely, the curcumin diet significantly increased fecal TG and TC. The curcumin diet up-regulated hepatic CYP7A1 mRNA level by 2.16-fold, compared to control group p (P < 0.05). These findings suggested that the increases in the CYP7A1 gene expression may partially account for the hypocholesterolemic effect of curcumin.

Effects of Capsaicin on Lipid Catabolism in 3T3-L1 Adipocytes

Capsaicin (8‐methyl‐N‐vanillyl‐6‐nonenamide) is a pungent ingredient of red peppers, and has been reported to reduce body weight gain and adiposity in rodents. The present study investigated the effects of capsaicin on lipid catabolism in differentiated 3T3‐L1 adipocytes. Capsaicin decreased the intracellular lipid content in a concentration‐dependent manner. The release of glycerol into the medium was increased by the addition of capsaicin. The mRNA levels of genes involved in lipid catabolism such as hormone sensitive lipase (HSL), carnitine palmitoyl transferase‐Iα (CPTI‐α) and uncoupling protein 2 (UCP2) were up‐regulated significantly. These results suggest that capsaicin exerts its lipolytic action by increasing the hydrolysis of triacylglycerol in adipocytes, and that these effects are mediated at least partially by regulation of the expression of multiple genes that are involved in the lipid catabolic pathway, such as HSL and CPT‐Iα, and those involved in thermogenesis such as UCP2. Copyright

Ginsenoside RG3 reduces lipid accumulation with AMP-activated protein kinase (AMPK) activation in HepG2 cells

Cardiovascular disease (CVD) is one of the main causes of mortality worldwide, and dyslipidemia is a major risk factor for CVD. Ginseng has been widely used in the clinic to treat CVD. Ginsenoside Rg3, one of the major active components of ginseng, has been reported to exhibit antiobesity, antidiabetic, and cardioprotective effects. However, the effect of ginsenoside Rg3 on hepatic lipid metabolism remains unclear. Therefore, we investigated whether ginsenoside Rg3 would regulate hepatic lipid metabolism with AMP-activated protein kinase (AMPK) activation in HepG2 cells. Ginsenoside Rg3 significantly reduced hepatic cholesterol and triglyceride levels. Furthermore, ginsenoside Rg3 inhibited expression of sterol regulatory element binding protein-2 (SREBP-2) and 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR). Ginsenoside Rg3 increased activity of AMPK, a major regulator of energy metabolism. These results suggest that ginsenoside Rg3 reduces hepatic lipid accumulation with inhibition of SREBP-2 and HMGCR expression and stimulation of AMPK activity in HepG2 cells. Therefore, ginsenoside Rg3 may be beneficial as a food ingredient to lower the risk of CVD by regulating dyslipidemia.

Reduction of Body Weight by Dietary Garlic Is Associated with an Increase in Uncoupling Protein mRNA Expression and Activation of AMP-Activated Protein Kinase in Diet-Induced Obese Mice

This study investigated the antiobesity effect of garlic in diet-induced obese mice. Male C57BL/6J mice were fed a high-fat diet (45% fat) for 8 wk to induce obesity. Subsequently, they were fed a high-fat control diet, high-fat diets supplemented with 2%, or 5% garlic (wt:wt) for another 7 wk. Dietary garlic reduced body weight and the mass of various white adipose tissue deposits and also ameliorated the high-fat diet-induced abnormal plasma and liver lipid profiles. Garlic supplementation significantly decreased the mRNA levels of adipogenic genes in white adipose tissues (WAT). However, consumption of garlic increased the expression of mRNA for uncoupling proteins in brown adipose tissue (BAT), liver, WAT, and skeletal muscle. Mice treated with garlic maintained a significantly higher body temperature than untreated mice during a 6-h, 4°C cold challenge and, notably, AMP-activated protein kinase (AMPK) activity was stimulated in BAT, liver, WAT, and skeletal muscle. These results suggest that the antiobesity effects of garlic were at least partially mediated via activation of AMPK, increased thermogenesis, and decreased expression of multiple genes involved in adipogenesis.

Green tea catechin enhances cholesterol 7α-hydroxylase gene expression in HepG2 cells

Green tea catechins are known to have hypocholesterolaemic effects in animals and human subjects. In the present study, we investigated the effects of green tea catechins on the mRNA level and promoter activity of hepatic cholesterol 7alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in the conversion of cholesterol to bile acids, in human hepatoma cells. Real-time PCR assays showed that different catechins, (-)-epicatechin gallate (ECG), (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC) and (-)-epicatechin (EC), up regulated the CYP7A1 mRNA level by 5.5-, 4.2-, 2.9- and 1.9-fold, respectively, compared with the control. The -1312/+358 bp of the CYP7A1 promoter was subcloned into the pGL3 basic vector that includes luciferase as a reporter gene. ECG or EGCG significantly increased CYP7A1 promoter activity by 6.0- or 4.0-fold, respectively, compared with the control. Also, EGCG stimulated CYP7A1 at both mRNA level and promoter activity in a dose-dependent manner. These results suggest that the expression of the CYP7A1 gene may be directly regulated by green tea catechins at the transcriptional level.

Immobilized phospholipase A1-catalyzed modification of phosphatidylcholine with n-3 polyunsaturated fatty acid.

n-3 Polyunsaturated fatty acids (n-3 PUFA)-enriched phosphatidylcholine (PC) was successfully produced with fatty acid from fish oil and PC from soybean by immobilized phospholipase A1-catalyzed acidolysis. Detailed studies of immobilization were carried out, and Lewatit VP OC 1600 was selected as a carrier for preparation of immobilized phospholipase A1, which was used for modification of PC by acidolysis. For acidolysis of PC with n-3 PUFA, the effects of several parameters, namely, water content, temperature, and enzyme loading on the reaction time course were investigated to determine optimum conditions. The optimum water content, temperature, and enzyme loading were 1.0%, 55 °C, and 20%, respectively. The highest incorporation (57.4 mol%) of n-3 PUFA into PC was obtained at 24h and the yield of PC was 16.7 mol%. The yield of PC increased significantly by application of vacuum, even though a slight decrease of n-3 PUFA incorporation was observed.

Marginal zinc deficiency in rats decreases leptin expression independently of food intake and corticotrophin-releasing hormone in relation to food intake.

Zn deficiency reduces food intake and growth rate in rodents. To determine the relationship between Zn deficiency and the regulation of food intake, we evaluated leptin gene expression in epididymal white adipose tissue (eWAT), and hypothalamic corticotropin-releasing hormone (hCRH) and hypothalamic neuropeptide Y (hNPY) of rats Zn-deficient only to show reduced food intake and growth rate but not food intake cycling. Growing male Sprague-Dawley rats (240 g) were randomly assigned to one of four dietary groups: Zn-adequate (ZA; 30 mg/kg diet), Zn-deficient (ZD; 3 mg/kg diet), pair-fed with ZD (PF; 30 mg/kg diet) and Zn-sufficient (ZS; 50 mg/kg diet) (n 8), and were fed for 3 weeks. Food intake and body weight were measured, as were blood mononuclear cells and pancreas Zn levels. eWAT leptin, hCRH and hNPY mRNA levels were determined. Food intake was decreased by about 10 % in ZD and PF rats compared to ZA and ZS rats. Growth and eWAT leptin mRNA levels were unaffected in PF rats but were significantly (P < 0.05) decreased in ZD rats. However, hNPY showed a tendency to increase, and hCRH significantly (P < 0.05) decreased, in both ZD and PF rats. These results suggest that while leptin gene expression may be directly affected by Zn, hNPY and hCRH are likely responding to reduced food intake caused by Zn deficiency.

(−)-Epigallocatechin-3-gallate Enhances Uncoupling Protein 2 Gene Expression in 3T3-L1 Adipocytes

In this study, we investigated the effects of green tea (−)-epigallocatechin-3-gallate (EGCG) on the mRNA level and promoter activity of uncoupling protein 2 (UCP2), a mitochondrial membrane transporter that regulates energy expenditure and thermogenesis in 3T3-L1 adipocytes. EGCG up-regulated the UCP2 mRNA level in a dose-dependent manner. UCP2 promoter activity was significantly stimulated by EGCG treatment, to an extent similar to that seen in mRNA expression. These results suggest that expression of UCP2 gene is directly regulated by green tea EGCG, which is mediated through the transcriptional activation of its proximal promoter.