• Food Science and Preservation
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• v.22 no.1
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• pp.27-35
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• 2015

Anti-obese effects of mulberry (Morus alba L.) root bark was investigated in vitro by measuring its inhibitory effect against 3T3-L1 preadipocyte differentiation and digestive enzymes such as ${\alpha}$-amylase, ${\alpha}$-glucosidase and pancreatic lipase. Ethanol extract of mulberry root bark (MRE) showed the potent inhibitory activities on ${\alpha}$-amylase, ${\alpha}$-glucosidase and pancreatic lipase with $IC_{50}$ values of $7.86{\pm}0.36$, $0.12{\pm}0.03$ and $7.93{\pm}0.11mg/mL$, respectively. Furthermore, MRE significantly suppressed cellular lipid accumulation in 3T3-L1 cells in a dose-dependent manner. To elucidate the mechanism of MRE, we performed qRT-PCR and Western blotting for the expression of genes related with adipogenesis and lipogenesis. Treatment of MRE markedly suppressed the protein expression of $PPAR{\gamma}$, $C/EBP{\alpha}$ and SREBP-1c, as well as FAS and ACC, which are the key transcription factors and metabolic enzymes in adipogenesis and lipogenesis. In addition, qRT-PCR analysis indicated that the anti-adipogenesis effect of MRE might be due to its inhibition at transcription levels. These results demonstrate that MRE can effectively suppress adipocyte differentiation and inhibit key enzymes related to obesity. Our findings suggest that mulberry root bark may have a potential benefit in preventing obesity.

• Journal of Life Science
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• v.21 no.9
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• pp.1301-1309
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• 2011

The major function of adipocytes is to store fat in the form of triglycerides. One of the signaling pathways known to affect adipogenesis, i.e. fat formation, is the WNT/${\beta}$-catenin pathway which inhibits the expression and activity of key regulators of adipogenesis. The purpose of this research is to find genes among the WNT/${\beta}$-catenin pathway which regulate adipogenesis by using small interfering (si) RNA and to find the association of single nucleotide polymorphisms (SNPs) of the gene with serum triglyceride levels in the human population. To elucidate the effects of ${\beta}$-catenin siRNA on adipogenesis key factors, PPAR${\gamma}$ and C/EBP${\alpha}$, we performed real-time PCR and western blotting experiments for the analyses of mRNA and protein levels. It was found that the siRNA-mediated knockdown of ${\beta}$-catenin upregulates adipogenesis key factors. However, upstream regulators of the WNT/${\beta}$-catenin pathway, such as DVL2 and LRP6, had no significant effects compared to ${\beta}$-catenin. These results indicate that ${\beta}$-catenin is a candidate gene for human fat accumulation. In general, serum triglyceride level is a good indicator of fat accumulation in humans. According to statistical analyses of the association between serum triglyceride level and SNPs of ${\beta}$-catenin, -10,288 C>T SNP (rs7630377) in the promoter region was significantly associated with serum triglyceride levels (p<0.05) in 290 Korean subjects. On the other hand, serum cholesterol levels were not significantly associated with SNPs of the ${\beta}$-catenin gene. The results of this study showed that ${\beta}$-catenin is associated with fat accumulation both in vitro and in the human population.

• Korean Journal of Poultry Science
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• v.42 no.3
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• pp.231-238
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• 2015

The present study aimed to investigate the effects of lycopene on hepatic metabolic- and immune-related gene expression in laying hens. A total of 48 25-week-old White Leghorn hens were randomly allocated into four groups consisting of four replicates of three birds: control (basal diet), T1 (basal diet + 10 mg/kg of tomato powder-containing lycopene), T2 (basal diet + 10 mg/kg of micelles of tomato powder-containing lycopene), and T3 (basal diet + 10 mg/kg of purified lycopene). Chickens were fed ad libitum for 5 weeks, and then total RNA was extracted from the livers for quantitative RT-PCR analysis. Peroxisome proliferator-activated receptor ${\gamma}$ (PPAR${\gamma}$) expression was decreased in the liver of chickens after lycopene supplementation (P<0.05). Micellar lycopene supplementation decreased the expression of PPAR${\gamma}$ target genes including fatty acid binding protein 4 (FABP4) and fatty acids synthase (FASN) in the T2 group (P<0.05). Sterol regulatory element-binding protein 2 (SREBP2) and C/EBP-${\alpha}$ were also downregulated in hens fed with micellar lycopene (P<0.05). Glucose transporter 8 (GLUT-8) was upregulated in the T2 and T3 groups (P<0.05). However, the expression of carnitine palmitoyltransferase 1 (CPT-1) was not changed by lycopene supplementation. Pro-inflammatory cytokines such as tumor necrosis factor ${\alpha}$ (TNF-${\alpha}$) and interleukin 6 (IL-6) were downregulated by lycopene supplementation (P<0.05). These data suggest that the type of lycopene supplementation is critical and that micelles of tomato powder-containing lycopene may play an important role in the modulation of lipid metabolism and immunity in chickens.

• Journal of Life Science
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• v.29 no.1
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• pp.60-68
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• 2019

Limonium tetragonum, an edible halophyte that grows on salt marshes in Korea, is thought to possess various health benefits (e.g., antioxidant, antitumor, and hepatoprotective). In the present study, different solvent partitioned subfractions, water ($H_2O$), buthanol (n-BuOH), 85% aqueous methanol (85% aq. MeOH), and hexane (n-hexane), from crude extract of L. tetragonum were tested for their ability to prevent adipogenesis in differentiating 3T3-L1 preadipocytes. The treatment of differentiating 3T3-L1 preadipocytes with L. tetragonum subfractions (LTFs) resulted in suppressed adipogenesis and reduced expression of adipogenesis-related transcription factors such as peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$), CCAATT/enhancer-binding protein alpha ($C/EBP{\alpha}$), and sterol regulatory element-binding protein 1c (SREBP-1c) at both mRNA and protein levels. In addition, the LTF treatment notably decreased the levels of phosphorylated p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) of the mitogen-activated protein kinase (MAPK) pathway in association with $PPAR{\gamma}$-linked adipogenesis. Among all the tested LTFs, $H_2O$ and n-hexane were the most effective in lowering lipid accumulation and regulating the adipocyte differentiation via $PPAR{\gamma}$ pathway. Taken together, the results indicated that the $H_2O$ and n-hexane LTFs contain bioactive compounds that may exhibit significant antiadipogenesis activity by downregulation of the $PPAR{\gamma}$ pathway and inactivation of the MAPK signal pathway in 3T3-L1 preadipocytes.

• Journal of Life Science
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• v.32 no.11
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• pp.855-864
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• 2022

The pharmacological efficacy of Dipterocarpus tuberculatus Roxb. has been verified in only several fields including photoaging, inflammation, hepatotoxicity, acute gastritis and osseointegration. To identify the novel functions of Dipterocarpus tuberculatus Roxb. on anti-obesity, inhibitory effect on lipid accumulation and stimulatory effect on lipolysis were investigated in MDI (3-isobutyl-1-methyl-xanthine, dexamethasone, and insulin) stimulated 3T3-L1 adipocytes treated with methanol extracts of Dipterocarpus tuberculatus Roxb. (MED). Lipogenic targets, including lipid accumulation, level of lipogenic transcription factors, and expression of lipogenic regulators, were downregulated in MDI-stimulated 3T3-L1 adipocytes treated with MED without any significant cytotoxicity. Also, MED treatment inhibited the mRNA levels of adipogenic targets including peroxisome proliferator-activated receptor (PPAR)γ and CCAAT-enhancer binding protein (C/EBP) α, as well as lipogeic targets including adipocyte fatty acid binding protein 2 (aP2) and fatty acid synthetase (FAS) in MDI-stimulated 3T3-L1 adipocytes. A similar decrease patterns were detected in Oil red O stained lipid droplets of MED treated MDI-stimulated 3T3-L1 adipocytes. Furthermore, several lipolytic targets, such as cAMP concentration, concentration of free glycerol, expression level of lipases, including ATGL, perilipin and HSL, were upregulated in MDI-stimulated 3T3-L1 adipocytes treated with MED. These results show that MED has a novel role as a lipogenesis inhibitor and lipolysis stimulator in MDI-stimulated 3T3-L1 adipocytes.

• Journal of Life Science
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• v.34 no.2
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• pp.113-121
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• 2024

Endoplasmic reticulum (ER) stress responses are markedly induced during toxic responses caused by various chemical substances, including difenoconazole, but no research has been conducted on 1,2,3-trichloropropane (TCP), a chemical that is generally used in agriculture and industry, which induces hepatotoxicity. Therefore, in this study, the changes in indicators for hepatotoxicity, apoptosis, and ER stress were analyzed in TCP-treated Sprague Dawley (SD) rats to study the regulatory mechanism of ER stress during the hepatotoxicity. The TCP-treated group decreased in body weight and dietary intake compared to the vehicle-treated group, and necrosis and vacuolation increased significantly in liver histology. In addition, the expression of apoptosis-related factors, including Bax/Bcl-2 and cleaved caspase (Cas)-3/Cas-3 increased significantly in the TCP-treated group compared to the vehicle-treated group. In the analysis of ER stress response indicators, the expression of C/EBP homologous protein (CHOP), phospho-eukaryotic translation initiation factor 2 alpha subunit (eIF2α), and phospho-inositol-requiring enzyme 1α (IRE1α) increased only in the TCP100-treated group and decreased in the TCP200-treated group. However, the transcriptions of growth arrest and DNA damage-34 (GADD34) increased in the TCP200-treated group, while Spliced X-box binding protein-1 (XBP1s) and unspliced XBP1(XBP1u) decreased in the same group. These results suggest that the ER stress response is successfully triggered during the hepatotoxicity induced by TCP treatment through the alternative regulation of the unfolded-protein response (UPR) pathway.

• BMB Reports
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• v.49 no.2
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• pp.111-115
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• 2016

Caffeine has been proposed to have several beneficial effects on obesity and its related metabolic diseases; however, how caffeine affects adipocyte differentiation has not been elucidated. In this study, we demonstrated that caffeine suppressed 3T3-L1 adipocyte differentiation and inhibited the expression of CCAAT/enhancer binding protein (C/EBP)α and peroxisome proliferator-activated receptor (PPAR)γ, two main adipogenic transcription factors. Anti-adipogenic markers, such as preadipocyte secreted factor (Pref)-1 and Krüppel-like factor 2, remained to be expressed in the presence of caffeine. Furthermore, 3T3-L1 cells failed to undergo typical mitotic clonal expansion in the presence of caffeine. Investigation of hormonal signaling revealed that caffeine inhibited the activation of AKT and glycogen synthase kinase (GSK) 3 in a dose-dependent manner, but not extracellular signal-regulated kinase (ERK). Our data show that caffeine is an anti-adipogenic bioactive compound involved in the modulation of mitotic clonal expansion during adipocyte differentiation through the AKT/GSK3 pathway.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.4
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• pp.474-483
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• 2016

Enzymatically modified isoquercitrin (EMIQ) is a mixture of quercetin glycodsides consisting of isoquercitrin and its ${\alpha}-glucosylated$ derivatives containing one to seven additional linear glucose moieties. The aim of this study was to assess whether or not EMIQ attenuates high-fat diet (HFD)-induced body weight gain and changes in plasma indices of obesity in mice. Male C57BL/6N mice were fed chow diet, HFD, and HFD containing 1.2% EMIQ for 10 weeks. EMIQ significantly (P<0.05) reduced body weight gain (-21%), total visceral fat-pad weights (-31%), and plasma levels of triglycerides (-17%), total cholesterol (-19%), and free fatty acids (-26%) in HFD-fed mice. EMIQ significantly increased protein kinase A (PKA) expression in the epididymal adipose tissue of HFD-fed mice. Expression of adipogenesis-related genes significantly decreased, whereas expression of fatty acid oxidation-related and thermogenesis-related genes increased in epididymal adipose tissue of EMIQ-fed mice compared with HFD-fed mice. These results suggest that the protective effects of EMIQ against HFD-induced adiposity in mice appear to be associated with PKA-mediated signaling cascades involved in adipogenesis, fatty acid oxidation, and thermogenesis in adipose tissue.

• KSBB Journal
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• v.24 no.6
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• pp.549-555
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• 2009

4 kinds of Regional Special Natural Products (RSNPs), such as Anthrisci radix, Psoraleae semen, Siegesbeckiae herba and Corni fructus were examined to verify for anti-obesity effect. $PPAR\gamma$ (peroxisome proliferator-activated receptor $\gamma$) from 3T3-L1 cell concerning adipocyte differentiation was suppressed by different concentraton of 4 RSNPs with western blot, when treated RSNPs' extract and MDI (IBMX, Dexamethasone, Insulin) at the same time. Also, SREBP-1 (Sterol regulatory element binding protein) controlling lipogenesis and $PPAR\gamma$ expression levels were reduced by these 4 RSNPs' extract, when these chemicals after differentiation of 3T3-L1 cell. And lipid droplets were reduced by 7.5%, 14.4%, 18.3% and 30% at different concentration of Anthrisci radix from Oil Red O staining. Also, it was reduced by 2%, 4.9%, 9.3% and 38% at different concentration of Psoraleae semen. For Siegesbeckiae herba, it was inhibited by 1.4%, 6.4%, 16.4% and 30.1%, respectively. And Corni fructus was also showed by 0.9%, 6.3%, 13.7% and 33% at same concentration of Siegesbeckiae herba. These 4 kinds of RSNPs were expected for a useful material for anti-obesity materials.

• Journal of Acupuncture Research
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• v.27 no.6
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• pp.31-42
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• 2010

Objectives : The aim of this study was to investigate the anti-obesity potential and mechanisms of action of Rhizoma Atractylodis(RA) herbal acupuncture in high fat diet- induced obese ICR mice. Methods : Sample solutions for herbal acupuncture were prepared from the Rhizoma Atractylodis water extract powder at concentration of 150mg/kg and 300mg/kg with distilled water. Five week-old ICR mice acclimatized to the laboratory environment for 1 week were allocated into four groups: regular diet group (RD), high fat diet group(HFD), groups fed HFD with 150mg/kg RA herbal acupuncture treatment (RAE 150) and with 300mg/kg RA herbal acupuncture treatment(RAE 300). Herbal acupuncture groups were injected with either 150mg/kg or 300mg/kg of Rhizoma Atractylodis(RA) subcutaneously onto both Sinsu($BL_{23}$) alternately on the same time everyday for 30days. Body weight, gross appearance of epididymal fat area, blood glucose, insulin, insulin resistance(HOMA-IR), non-esterified fatty acid, cholesterol, triglyceride, AST, ALT, histological analysis of white adipose tissue, gene expression responsible for adipocyte differentiation and AMPK activation were analyzed. Results : RA herbal acupuncture inhibited the development of weight gain, hyperglycemia, hyperinsulinemia, hyperlipidemia, increases of AST and ALT, and the enlargement of fat cell size induced by HFD. Also, RA herbal acupuncture inhibited the expression of PPAR-${\gamma}$, C/$EBP{\alpha}$, aP2, LPL, FAS, SCD-1 and enhanced the activation of AMP-activated protein kinase. Conclusions : The results of this study demonstrate that RA herbal acupuncture can exert the anti-obesity effect and it is partially mediated by activation of AMPK and inhibition of the gene expressions responsible for adipocyte differentiation. Further studies will be required to ascertain the nti-obesity effect and mechanisms of action of RA herbal acupuncture in animal models and human for aclinical application.