• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.4
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• pp.484-491
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• 2016

The present study investigated the effect of Sinetrol-XPur (polyphenolic Citrus spp. and Paullinia cupana Kunth dry extract) and defined the action mode for cyclic adenosine monophosphate (cAMP)-dependent uncoupling protein (UCP)-2 activation. Leptin-deficient obese mice were treated with two different doses, 100 mg/kg body weight (BW) and 300 mg/kg BW of each AIN93G supplement, for 7 weeks. Treatment of obese mice with both low and high doses of Sinetrol-XPur significantly reduced body weight gain compared to control obese mice. White adipose tissue weight of mice was reduced by 30.96% in high dose-supplemented groups. Serum total cholesterol and triglyceride were reduced by a high dose of Sinetrol-XPur by 20.02% and 30.96%, respectively. Serum level of high density lipoprotein (HDL) was significantly increased by treatment with both doses, as the ratio of HDL to low density lipoprotein increased by 138.78% and 171.49%, respectively. Regarding expression of biochemical factors related to lipid metabolism, fatty acid synthase significantly decreased and UCP-2 increased upon treatment with a high dose of Sinetrol-XPur, but there was no significant difference in lipoprotein lipase and hormone-sensitive lipase. To define cellular mechanism, intracellular cAMP levels in 3T3-L1 adipocytes significantly increased in a dose-dependent manner over the range of $50{\sim}250{\mu}m/mL$. The phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine clearly blocked cAMP, suggesting that Sinetrol-XPur promotes lipolysis of adipocytes through inhibition of cAMP-dependent PDE, resulting in induction of cAMP response element binding protein and UCP-2. These results suggest that Sinetrol-XPur supplementation is a viable option for reducing body weight and fat by improving serum lipid profiles and genetic expression of lipid metabolic factors, especially activation of cAMP-dependent UCP-2.

• 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.

• Korean Journal of Food Science and Technology
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• v.48 no.4
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• pp.384-391
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• 2016

In previous studies, we confirmed that the ethanol extract of Polygonatum sibiricum (ID1216) has anti-obesity effects on high-fat diet-fed mice. To identify the obesity-related genes affected by ID1216, we studied its effects both in vivo and in vitro. In mice, single administration of ID1216 increased the expression of obesity-related genes including sirtuin1 (SIRT1), peroxisome proliferator-activated receptor ${\gamma}$ coactivator $1{\alpha}$ ($PGC1{\alpha}$) and peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) compared to that in mice administered the vehicle; their downstream genes (uncoupling proteins, acyl-CoA oxidase, adipocyte protein 2, and hormone-sensitive lipase) were also increased by ID1216. In fully differentiated 3T3-L1 adipocytes, ID1216 showed the same effects on anti-obesity genes as those in the animal model. Based on these results, we propose that ID1216 has anti-obesity effects by regulating the $SIRT1-PGC1{\alpha}-PPAR{\alpha}$ pathway and their downstream genes, thereby controlling energy and lipid metabolisms.

• Journal of Korean Medicine Rehabilitation
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• v.32 no.2
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• pp.19-36
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• 2022

Objectives This study is to investigate the effects and mechanisms of Imyo-san (IMS) on the obese mice model induced by high-fat diet. Methods Antioxidative capacity was measured by in vitro method. C57BL/6 mice were randomly assigned into 5 groups (n=7). Normal group was fed general diet (Normal). The other 4 groups were fed high fat diet (HFD) with water (Control), with Garcinia gummi-gutta (GG, Garcinia gummi-gutta 200 mg/kg), with low-dose IMS (IMSL, Imyo-san 0.54 g/kg) and with high-dose IMS (IMSH, Imyo-san 1.08 g/kg). Results IMS showed high radical scavenging activity. After 6 week experiment, body weight, food intake, food efficiency ratio (FER), epididymal fat and liver weight, triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, sterol regulatory element-binding protein-1 (SREBP-1), phospho-acetyl-CoA carboxylase (p-ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), SREBP-2, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), phospho-liver kinase B1 (p-LKB1), phospho-AMP-activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor 𝛼 (PPAR𝛼), peroxisome proliferator-activated receptor 𝛾 coactivator-1𝛼 (PGC-1𝛼), uncoupling protein-2 (UCP-2), carnitine palmitoyltransferase 1A (CPT-1A), and histology of liver and epididymal fat were measured and analysed. Body weight gain, FER, liver and epididymal fat weight of IMS groups were significantly decreased. There were significant improvements in blood lipids with less TG, TC, LDL-cholesterol, VLDL-cholesterol and more HDL-cholesterol. Proteins associated with lipid synthesis (SREBP-1, p-ACC, FAS, SCD-1) and cholesterol (SREBP-2, HMGCR) was improved. Factors regulating lipid synthesis and lipid catabolism (p-LKBI, p-AMPK, PPARα, PGC-1α, UCP-2, CPT-1A) were increased. In histological examinations, IMS group had smaller fat droplets than control group. All results increased depending on concentration. Conclusions It can be suggested that IMS has anti-obesity effects with improving lipid metabolism.

• The Korean Journal of Food And Nutrition
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• v.29 no.4
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• pp.506-512
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• 2016

Bitter melon (Momordica charantia) is used in traditional herbal medicine in many Asian countries for the treatment of several diseases such as diabetes, eczema, night blindness, psoriasis, and rheumatism. Especially, most reports concerning the biological activities of bitter melon have focused on its effects on diabetes and hyperglycemia. Also, bitter melon is regarded as a longevity food, suggesting that it has several beneficial effects on anti-aging and the maintenance of a healthy state. Thus, we investigated whether bitter melon could increase the capacity of exercise in this study. Interestingly, bitter melon fruit extract activated AMP-activated protein kinase (AMPK), which is important for regulating glucose homeostasis, mitochondrial content and exercise capacity. In addition, bitter melon extract increased the expression of enzymes involved in fatty acid oxidation such as mitochondrial uncoupling protein 3 (UCP3), carnitine palmitoyl transferase 1b (CPT1b), and pyruvate dehydrogenase lipoamide kinase isozyme 4 (PDK4). Moreover, exercise tolerance was much more enhanced in bitter melon treated animals compared to the non-treated control group. These results suggest that bitter melon is a promising candidate for the development of functional foods beneficial for physical strength and the enhancement of exercise capacity.

• Environmental Mutagens and Carcinogens
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• v.22 no.1
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• pp.39-46
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• 2002

Obesity is a complex metabolic disorder with a strong genetic component. There are many candidate genes for obesity and its related phenotypes. We studied genetic variations between Korean obese and lean groups. Polymorphisms investigated were the Msp I polymorphism of the $\alpha$$_{2A}$-adrenergic receptor ($\alpha$$_{2A}$-AR) gene, the Mnl I polymorphism of the $\alpha$$_2$-adrenergic receptor ($\alpha$$_2$-AR) gene, the BstO I polymorphism of the $\beta$$_3$-adrenergic receptor ($\beta$$_3$-AR) gene, the Pml I polymorphism of the lamin A/C (LMNA) gene, the Hga I polymorphism of the clearance receptor (NPRC) gene, the Msp I polymorphism of the leptin gene, BclI polymorphism of the uncoupling protein 1 (UCPI) gene and the Hha I polymorphism of the fatty acid binding protein 2 (FABP2) gene. Among these genetic markers, Pml I polymorphism at the LMNA gene and Bcl I polymorphism at the UCP1 gene were significantly associated with obesity. However, further studies are required whether thease findings are reproduced in large population, although two polymorphisms might be useful as genetic markers in the ethiology of obesity in Korean population.ion.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.2
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• pp.31-48
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• 2011

Objectives : In order to investigate the anti-obesity effects of Wolbi-tang(here in after referred to WBT) on the obese gene and obese inhibitory, C57BL/6 mice were induced by high-fat diet. Methods : C57BL/6 mice were divided into 5 groups(normal, only high-fat diet, high-fat diet with Reductil, high-fat diet with WBT 400, 200 mg/kg extract) and fed for 5 weeks. And observed body weight change, total cholesterol, low density lipoprotein cholesterol(LDL-cholesterol), high density lipoprotein cholesterol (HDL-cholesterol), triglyceride, glucose, leptin change, alanine transaminase(ALT), aspartate transaminase(AST), serum creatinine, the expression of ${\beta}3$-adrenergic receptor(${\beta}3AR$), leptin, uncoupling protein(UCP2) gene in 3T3-L1 adipocyte, 3T3-L1 adipocyte proliferation, histological analysis of adipose tissue and liver tissue. Results : 1. Refer to cell cytotoxicity, viability of human fibroblast cells(hFCs) showed not significant changes. 2. The amount of ALT, AST was decreased significantly in WBT 400 mg/kg, 200 mg/kg groups. The amount of creatinine showed not significant changes. 3. Body weight was decreased significantly in WBT 400 mg/kg, 200 mg/kg groups. 4. The amount of total cholesterol and triglyceride was decreased significantly in WBT 400 mg/kg, 200 mg/kg groups. LDL-cholesterol was decreased and HDL-cholesterol was increased significantly in WBT 400 mg/kg groups. 5. The amount of glucose was decreased significantly in WBT 400 mg/kg groups. 6. The amount of serum leptin was decreased significantly in WBT 400 mg/kg, 200 mg/kg groups. 7. The revelation of ${\beta}3AR$ in 3T3-L1 adipocyte was increased significantly in WBT $100{\mu}g/ml$, $50{\mu}g/ml$ groups. The revelation of leptin was decreased significantly in WBT $100{\mu}g/ml$, $50{\mu}g/ml$ groups. The revelation of UCP2 was decreased significantly in WBT $100{\mu}g/ml$ group. 8. 3T3-L1 adipocyte proliferation was decreased significantly in WBT $100{\mu}g/ml$, $50{\mu}g/ml$ groups. The size of adipocyte was decreased relative to the control group in WBT 400 mg/kg group. 9. The adipose vacuoles in liver tissue was decreased relative to the control group. Conclusions : These results suggested that WBT has inhibitory effects of obesity. WBT might be applicated on treatment of obesity and metabolic syndrome. Further studies analysing its effects were needed.

• Journal of Nutrition and Health
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• v.55 no.4
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• pp.462-475
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• 2022

Purpose: Allomyrina dichotoma larvae are one of the approved edible insects with nutritional value and various functional and medicinal properties. Previously we have demonstrated that the Allomyrina dichotoma larval extract (ADLE) ameliorates hepatic insulin resistance in high-fat diet (HFD)-induced diabetic mice through the activation of adenosine monophosphate-activated protein kinase (AMPK). This study investigated the effects of ADLE on insulin resistance in the skeletal muscle and explored mechanisms for enhancing the glucose uptake in palmitate (PAL)-treated C2C12 myotubes. Methods: To induce insulin resistance, the differentiated C2C12 myotubes were treated with PAL (0.5 mM) for 24 hours, and then treated with a 0.5 mg/ml concentration of ADLE, and the resultant effects were measured. The expression levels of glucose transporter-4 (GLUT4), AMPK, and the mitochondrial metabolism-related proteins were analyzed by western blotting. The mRNA expression levels of lipogenesis- related genes were determined by quantitative reverse-transcriptase PCR. Results: The exposure of C2C12 myotubes to 0.5 mg/ml of ADLE increased cell viability significantly compared to PAL-treated cells. ADLE upregulated the protein expression of GLUT4 and enhanced glucose uptake in the PAL-treated cells. ADLE increased the phosphorylated AMPK in both the PAL-treated C2C12 myotubes and HFD-treated skeletal muscle. The reduced expression levels of peroxisome-proliferator-activated receptor gamma co-activator-1 alpha (PGC1α) and uncoupling protein 3 (UCP3) due to the PAL and HFD treatment were reversed by the ADLE treatment. The citrate synthase activity was also significantly increased with the PAL and ADLE co-treatment. Moreover, the mRNA and protein expressions of fatty acid synthesis-related factors were reduced in the PAL and HFD-treated muscle cells, and this effect was significantly attenuated by the ADLE treatment. Conclusion: ADLE activates AMPK, which in turn induces mitochondrial metabolism and reduces fatty acid synthesis in C2C12 myotubes. Therefore, ADLE could be useful for preventing or treating insulin resistance of skeletal muscles in diabetes.