• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.383-387
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• 2006

To investigate the effect of GyeongshinhaeGihwan 1(GGT1) frequently used as an anti-obesity herbal medicine in oriental medicine on the expression of obesity-related genes, we measured the changes in mRNA levels of these genes by GGT1 in human growth hormone transgenic (hGHTg) obese female rats, and these effects by GGT1 were compared with those of reductil (RD), an anti-obesity drug approved by FDA. Rats received once daily oral administrations of autoclaved water, RD, or GGT1 for 8 weeks. At the end of study, rats were sacrificed and tissues were harvested. Total RNA from adipose tissue, liver and kidney was prepared and the mRNA levels for LPL (lipoprotein lipase), $PPAR{\gamma}$ (peroxisome proliferator activated receptor-gamma), $PPAR{\delta}$ (peroxisome proliferator activated receptor-delta), leptin, $TNF{\alpha}$ (tumor necrosis factor-alpha), and internal standard G3PDH (glyceraldehyde-3-phosphate dehydrogenase) were analyzed by RT-PCR. Compared with control group, $PPAR{\gamma}$ mRNA levels of liver and kidney were decreased in both RD and GGT1 groups, and the effects were more prominent in GGT1 group than in RD group, suggesting that GGT1 is effective in the inhibition of lipid storage by decreasing the $PPAR{\gamma}$ expression. $PPAR{\delta}$ mRNA levels of adipose tissue were increased by RD and GGT1 compared with DW, and the magnitude of increase were higher in GGT1 group than in RD group, indicating that GGT1 stimulates fatty acid oxidation and energy metabolism by activating $PPAR{\delta}$ expression. GGT1 group had higher concentrations of serum leptin, a well-known inhibitor of appetite, than control and RD groups. However, The mRNA levels of leptin, LPL, and $TNF{\alpha}$ were not changed by GGT1. These results indicate that GGT1 can prevent obesity in hGHTg obese female rats by down-regulating and up-regulating the mRNA expression of $PPAR{\gamma}$ and $PPAR{\delta}$, respectively, and that this anti-obesity effects were more pronounced in GGT1 group compared with RD group. In addition, GGT1 seems to inhibit obesity by increasing the circulating leptin levels.

• Journal of Yeungnam Medical Science
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• v.24 no.2
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• pp.252-261
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• 2007

Background : Obesity is the most common nutritional disorder in Western society as well as in Korea. Obesity results from a combination of genetic, environmental, and behavioral factors. Materials and Methods : In an attempt to investigate the association of obesity with its candidate genes, ${\beta}3$ adrenergic receptor (${\beta}_3AR$) and uncoupling protein 2 (UCP2), we analyzed polymorphisms of ${\beta}_3AR$ Trp64Arg and UCP2 -866G/A by PCR-RFLP analysis and the obesity-related phenotypes, including body mass index (BMI), fasting glucose concentration, and plasma lipid profiles in 750 subjects. Results : The Trp64Arg polymorphism in the ${\beta}_3AR$ gene was not statistically associated with the BMI. The UCP2 -866G/A polymorphism was significantly higher in obese than in non-obese subjects (P<0.05). However, the UCP2 -866A/A polymorphism was higher in the non-obese subjects. Conclusion : These results suggest that the UCP2 -866G/A polymorphism might be more useful for the prediction of obesity and obesity-associated diseases in Korean patients than the ${\beta}_3AR$ Trp64Arg polymorphism.

• The Korea Journal of Herbology
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• v.26 no.1
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• pp.65-74
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• 2011

Objectives : This study was undertaken to verify the modulation mechanism of Gyeongshingangjeehwan18 (GGEx18) in ob/ob male mice. Methods : Eight-week old mice (wild-type C57BL/6J and ob/ob) were used for all experiments. Wild-type C57BL/6J mice were used as lean control and obese ob/ob mice were randomly divided into 5 groups : obese control, GGEx15 (Ephedra sinica Stapf + Rheum palmatum L.), GGEx16 (Ephedra sinica Stapf + Laminaria japonica Aresch), GGEx17 (Rheum palmatum L. + Laminaria japonica Aresch), and GGEx18 (Ephedra sinica Stapf + Laminaria japonica Aresch + Rheum palmatum L.). After mice were treated with several kinds of GGEx for 11 weeks, the mRNA expression of peroxisome proliferator-activated receptor (PPAR) target genes and uncoupling protein (UCP) were measured. In addition, $PPAR{\alpha}$ and $PPAR{\beta}$ transactivation was examined in NMu2Li hepatocytes, C2C12 myocytes, and 3T3-L1 preadipocytes using transient transfection assays. Results : 1. Hepatic $PPAR{\alpha}$ target genes, such as ACOX and VLCAD mRNA levels were significantly increased by GGEx18 compared with obese controls. In skeletal muscle, LCAD mRNA expression was stimulated by GGEx16, GGEx17, and GGEx18, whereas MCAD mRNA expression by GGEx17 and GGEx18. $PPAR{\beta}$ target LPL mRNA levels were also increased by GGEx16, GGEx17, and GGEx18 in skeletal muscle, but adipose LPL mRNA levels were decreased. In addition, GGEx18 upregulated UCP mRNA expression in skeletal muslce. 2. $PPAR{\alpha}$ reporter gene expression was increased by GGEx18 in NMu2Li cells compared with vehicle. $PPAR{\alpha}$ and $PPAR{\beta}$ reporter activities were also increased by all GGEx treatments in C2C12 and 3T3-L1 cells. Conclusions : These results suggest that GGEx can act as $PPAR{\alpha}$ and $PPAR{\beta}$ activators, and that GGEx may regulate obesity by stimulating $PPAR{\alpha}$, $PPAR{\beta}$, and UCP activity. Of the 4 compositions, GGEx18 seems to be most effective in improving obesity and lipid disorders.

• Nutrition Research and Practice
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• v.10 no.6
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• pp.629-634
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• 2016

BACKGROUND/OBJECTIVE: The aim of this experiments was to show anti-obesity effects of Korean solar salt from different salt fields in diet-induced obese mice. MATERIALS/METHODS: Diet-induced obesity (DIO) was induced by a high-fat diet (HFD; 45% cal from fat) in C57BL/6J mice for eight weeks. The mice were fed with the designated diets (chow diet for Normal, HFD for Control, 0.47%-salt-mixed HFD for purified salt (PS), Guerande solar salt from France (SS-G), solar salt from Y salt field (SS-Y), solar salts from T salt field (SS-T) and S salt field (SS-S)) for another eight weeks. We checked body weight, food efficiency ratio (FER) and tissue weights (liver and epididymal adipose tissue (EAT)), and observed serum concentrations of triacylglycerol (TG), total cholesterol (TC), leptin and insulin. We also evaluated gene expressions of adipogenic / lipogenic mRNAs of $C/EBP{\alpha}$, $PPAR{\gamma}$ and FAS and beta-oxidation-related factors ($PPAR{\alpha}$ and CPT-1) in liver and EAT. The mineral composition of salt samples were analyzed using inductively coupled plasma optical emission spectrometry (ICP-OES). RESULTS: SS-T and SS-S significantly reduced body weight gain, FER, and weight of EAT compared to control and other samples (P < 0.05). SS-T and SS-S also significantly decreased serum levels of TG, TC, leptin and insulin (P < 0.05). SS-T and SS-S suppressed expressions of adipogenic / lipogenic mRNAs in liver and EAT, while promoting expression of beta-oxidation-related factors. The lowest sodium concentration was observed in SS-T ($30.30{\pm}0.59%$), and the lowest sodium-to-potassium (Na/K) ratio was found in SS-S (17.81). CONCLUSIONS: Our study shows that well-processed Korean solar salt may have anti-obesity effects in vivo, probably owing to its differences in mineral composition and other components, presumably resulting from the manufacturing processes. Further research is needed into the mechanism and to explore optimal manufacturing processes.

• Molecular & Cellular Toxicology
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• v.4 no.4
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• pp.318-322
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• 2008

Obesity is an increasing worldwide health problem that is strongly related to the imbalance of food intake and energy metabolism. It was well-known that several substances in the hypothalamus regulate food intake and energy metabolism. We planned an integrative study to elucidate the mechanism of the development of obesity. Firstly, to find candidate genes with the marvelous effect, the different expression in the hypothalamus between ob/ob and 48-h fasting mice was investigated by using DNA microarray technology. As a result, we found 3 genes [peroxisome proliferator activated receptor, gamma, coactivator 1 alpha (Ppargc1a), calmodulin 1 (Calm1), and complexin 2 (Cplx2)] showing the different hypothalamic expression between ob/ob and 48-h fasting mice. Secondly, a genetic approach on PPARGC1A gene was performed, because PPARGC1A acts as a transcriptional coactivator and a metabolic regulator. Two hundred forty three obese female patients with body mass index (BMI)${\geq}$25 and 285 control female subjects with BMI 18 to<23 were recruited according to the Classification of Korean Society for the Study of Obesity. Among the coding single nucleotide polymorphisms (cSNPs) of PPARGC1A, 2 missense SNPs (rs8192678, Gly482Ser; rs3736265, Thr612Met) and 1 synonymous SNP (rs3755863, Thr528Thr) were selected, and analyzed by PCR-RFLP and pyrosequencing. For the analysis of genetic data, chi-square ($X^2$) test and EH program were used. The rs8192678 was significantly associated with obese women (P<0.0006; odds ratio, 1.5327; 95% confidence interval, 1.2006-1.9568). Haplotypes also showed significant association with obese women ($X^2$=33.28, P<0.0008). These results suggest that PPARGC1A might be related to the development of obesity.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.1
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• pp.1-22
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• 2011

Objectives : This study was undertaken to verify the effects of Wolbigachul-tang1(WBCEx1) on obesity using high fat diet-induced male mice and to investigate the molecular mechanisms involved. Methods : 8-week old C57BL/6 mice were divided into 5 groups; lean control, obese control, WBCEx1, 2, 3. After mice were treated with WBCEx1(water extract), 2(30% ethanol extract), 3(water extract; Ephedra sinica Stapf., Gypsum fibrosum) for 12 weeks, body weight gain, feeding efficiency ratio, plasma lipid and glucose metabolism, the messenger RNA(mRNA) expression of peroxisome proliferator activated receptor(PPAR)$\alpha$ target genes were measured. In addition, $PPAR{\alpha}$ target gene expression was examined in liver, white adipose tissue and skeletal muscle. Results : 1. WBCEx1-treated mice had significantly lower body weight gain and feeding efficiency ratio. 2. Consistent with the effects on body weight gain, WBCEx1 decreased the weights of epididymal and retroperitoneal white adipose tissue, inguinal subcutaneous adipose tissue, and brown adipose tissue. 3. WBCEx1 significantly decreased plasma triglyceride and total cholesterol levels. 4. The size of adipocytes were significantly decreased by WBCEx1, whereas the adipocyte number per unit area was increased. Hepatic lipid accumulation was decreased by WBCEx1. 5. WBCEx1 did not affect the mRNA expression of $PPAR{\alpha}$ target genes in liver, adipose tissue, and skeletal muscle. 6. Plasma asparate aminotransferase(AST), alanine aminotransferase(ALT), blood urea nitrogen(BUN) and creatine concentrations were in the physiological range. Liver and kidney weights were significantly lower following WBCEx treatment compared with obese controls, indicating that WBCEx does not show any toxic effects on liver and kidney. Conclusions : These results suggest that WBCEx1-induced body weight reduction is associated with appetite control and mediated by a mechanism other than the activation of $PPAR{\alpha}$.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.12
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• pp.1689-1695
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• 2008

Leptin, the hormone product of the obese gene, is secreted predominately from white adipose tissue and regulates feed intake, energy metabolism and body composition. It has been considered a candidate gene for performance, carcass and meat quality traits in beef cattle. The objective of this study was to identify SNPs in the promoter region of the leptin gene and to evaluate the possible association of the SNP genotypes with carcass and meat quality traits in Korean cattle. We identified a total of 25 SNPs in the promoter region (1,208-3,049 bp upstream from the transcription start site) of the leptin gene, eleven (g.1508C>G, g.1540G>A, g.1545G>A, g.1551C>T, g.1746T>G, g.1798ins(G), g.1932del(T), g.1933del(T), g.1934del(T), g.1993C>T and g.2033C>T) of which have not been reported previously. Their sequences were deposited in GenBank database with accession number DQ202319. Genotyping of the SNPs located at positions g.2418C>G and g.2423G>A within the promoter region was performed by direct sequencing and PCR-SSCP method to investigate the effects of SNP genotypes on carcass and meat quality traits in Korean cattle. The SNP and SSCP genotypes from the two mutations of the leptin promoter were shown to be associated with the BF trait. The average BF value of animals with heterozygous SNP genotype was significantly greater than that of animals with the homozygous SNP genotypes for the g.2418C>G and g.2423G>A SNPs (p<0.05). Analysis of the combined genotype effect in both SNPs showed that animals with the AC SSCP genotype had higher BF value than animals with BB or AA SSCP genotypes (p<0.05). These results suggest that SNP of the leptin promoter region may be useful markers for selection of economic traits in Korean cattle.

• Korean Journal of Plant Resources
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• v.29 no.1
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• pp.1-10
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• 2016

Obesity is a pro-inflammatory state that contributes to the development of metabolic disorders such as hyperlipidemia, insulin resistance, type 2 diabetes, non-alcoholic fatty liver, and cardiovascular disease. In this study, we evaluated the inhibition of adipogenesis in 3T3-L1 cells and in high-fat diet (HFD)-induced obese mice by Peucedanum japonicum Thunberg L. water extract (PJT). Lipid accumulation measurement indicates that PJT markedly inhibited adipogenesis in a dose-dependent manner. RT-PCR results demonstrated that the mRNA expression of adipogenic transcription factors such as peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein-α (C/EBPα) in 3T3-L1 cells were significantly down-regulated by PJT treatment. Oral administration of PJT (100, 300, and 500 ㎎/㎏, b.w/daily for 4 weeks) was conducted in high-fat diet induced obese mice and C57BL/6 mice. The PJT-administered group of HFD-induced mice had a lower body weight gain, along with decreased serum levels of glucose, triglycerides, and total cholesterol compared with the control mice, however, the HDL-cholesterol/total cholesterol ratio was increased. Furthermore, the elevated mRNA expression levels of adipogenesis related genes in the white adipose tissue of obese mice were significantly suppressed by PJT. These results indicate that PJT exhibits anti-obesity effects in obese mice by decreasing in serum lipid levels and lipogenesis related gene.

• Journal of the Korean Magnetic Resonance Society
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• v.16 no.1
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• pp.34-45
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• 2012

Melanocortin-4 receptor (MC4R) subtype is associated with obese humans. Especially, in a patient with severe early-onset obesity, novel heterozygous mutation in the MC4R gene was detected, resulting in an exchange of aspartic acid to asparagine in $90^{th}$ amino acid residue located in the predicted second trans-membrane domain (TM2). Mutations in the melanocortin-4 receptor (MC4R) gene are the most frequent monogenic causes of severe obesity which have been described as heterozygous with loss of function. In order to compare structure difference between MC4R wild type (MC4R-TM2-wt) and mutant (MC4R-TM2-D90N), we designed both MC4R-TM2-wt and MC4R-TM2-D90N construct in pET 21b vector. In this study, we optimized high-yield purification procedure for recombinant TM2-D90N. Eluted recombinant protein was resolubilized under urea condition for thrombin cleavage reaction and we conducted the high-performance liquid chromatography (HPLC) with reverse phase column under 1% acetonitrile, 0.01% TFA buffer solution. The molecular size of purified target peptide was confirmed by Tricine-SDS page analysis. To characterize MC4R-TM2-D90N, we have performed $^{15}N$-isotope labeling of peptide using M9 media and purified labeled target peptide for hetero-nuclear NMR spectroscopy.

• The Journal of Internal Korean Medicine
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• v.34 no.1
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• pp.1-13
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• 2013

Objectives : The purpose of this study was to investigate the effects of Jowiseungcheung-tang (JWSCT) extract on the lipid metabolism, anti-oxidation and inflammatory reflex. Methods : Male Sprague-Dawley rats were fed a high fat diet for 8 weeks and were randomly divided into 4 groups (10 mice in each group): control group, 100 mg/kg JWSCT group, 200 mg/kg JWSCT group, 300 mg/kg JWSCT group. The control group was administered 100 mg/kg of water, but the other three groups were administered 100, 200, 300 mg/kg JWSCT extract for 4 weeks. After 4 weeks, we measured lipid level, thiobarbituric acid reactive substance (TBARS), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and cytokines in plasma and liver. The gene expression level and the ratio of apo-B and apo-E were then investigated by way of reverse transcription -polymerase chain reaction (RT-PCR). Results : In the JWSCT group, compared with the control, free fatty acid, triglyceride, total cholesterol, LDL-cholesterol, TBARS, IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ decreased significantly in plasma and liver. However HDL-cholesterol, IL-10, GSH-Px, SOD and CAT increased. In the JWSCT group, compared with the control, the gene expression level and the ratio of apo-A and apo-E decreased significantly in the RT-PCR analysis. Conclusions : The extract of JWSCT has anti-obesity, anti-inflammatory and anti-oxidant effects.