• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.9
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• pp.1159-1165
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• 2006

Our preliminary study showed that genistein and daidzein improved blood glucose level in type 2 diabetic mice by enhancing the glucose and lipid metabolism. The objective of this study was to evaluate whether genistein and daidzein are associated with alterations in antioxidant defense mechanism of type 2 diabetic mice. Male C57BL/KsJ-db/db (db/db) mice and age-matched non-diabetic littermates (db/+) were used in this study. The db/db mice were divided into control, genistein (0.02%, w/w) and daidzein (0.02%, w/w) groups. The relative weights of liver, epididymal adipose tissue and perirenal adipose tissue were significantly higher in the db/db group than in the db/+ group, whereas heart weight was lower. The genistein and daidzein supplement did not affect the organ weights in db/db mice. The blood glucose level was positively correlated with superoxide dismutase (SOD, r=0.380, p<0.05) and catalase (CAT, r=0.345, p<0.05) activities and negatively correlated with glutathione peroxidase (GSH Px, r= 0.404, p<0.05) activity in erythrocyte. Therefore, the erythrocyte SOD and CAT activities were significantly elevated in the db/db group compared to the db/+ group and the GSH-Px activity was lowered. However, the supplementation of genistein and daidzein reversed erythrocyte CAT and GSH-Px activities in type 2 diabetic mice. In this current study, the SOD activities in liver, kidney and heart were significantly not different between the groups. The CAT and GSH-Px activities in liver and GSH-Px activity in kidney were significantly higher in the db/db group than in the db/+ group, while the CAT activity in kidney, CAT and GSH-Px activities in heart were lowered. The supplementation of genistein and daidzein significantly attenuated the changes of CAT and/or GSH-Px activities in liver and heart. The supplementation of genistein and daidzein elevated GSH levels in kidney and heart compared to the db/db control group. The lipid peroxide levels in liver, kidney and heart were significantly lowered in the genistein and daidzein supplemented groups compared to the db/db control group. These results suggest that genistein and daidzein might be beneficial for the prevention of type 2 diabetic complication via suppressing changes of antioxidant enzymes activities with simultaneous reduction of lipid peroxidation.

• Journal of Microbiology and Biotechnology
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• v.26 no.2
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• pp.295-308
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• 2016

This study investigated the effects of a flavonoid-rich ethanol extract of persimmon leaf (PL), an ethanol extract of Citrus junos Sieb (CJS), and a PL-CJS mixture (MPC) on mice fed a high-fat diet (HFD). We sought to elucidate the mechanisms of biological activity of these substances using measurements of blood coagulation indices and lipid metabolism parameters. C57BL/6J mice were fed a HFD with PL (0.5% (w/w)), CJS (0.1% (w/w)), or MPC (PL 0.5%, CJS 0.1% (w/w)) for 10 weeks. In comparison with data obtained for mice in the untreated HFD group, consumption of MPC remarkably prolonged the activated partial thromboplastin time (aPTT) and prothrombin time (PT), whereas exposure to PL prolonged aPTT only. Lower levels of plasma total cholesterol, hepatic cholesterol, and erythrocyte thiobarbituric acid-reactive substances, hepatic HMG-CoA reductase, and decreased SREBP-1c gene expression were observed in mice that received PL and MPC supplements compared with the respective values detected in the untreated HFD animals. Our results indicate that PL and MPC may have beneficial effects on blood circulation and lipid metabolism in obese mice.

• YAKHAK HOEJI
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• v.52 no.5
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• pp.345-354
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• 2008

This study was designed to investigate the anti-diabetic effect and mechanism of Korean red ginseng extract through transcriptomics in C57BL/KsJ db/db mice. The db/db mice were randomly divided into six groups: diabetic control group (DC), red ginseng extract low dose group (RGL, 100 mg/kg), red ginseng extract high dose group (RGH, 200 mg/kg), metformin group (MET, 300 mg/kg), glipizide group (GPZ, 15 mg/kg) and pioglitazone group (PIO, 30 mg/kg), and treated with drugs once per day for 10 weeks. At the end of treatment, we measured blood glucose, insulin, hemoglobin A1c (HbA1c), triglyceride (TG), adiponectin, leptin, non-esterified fatty acid (NEFA). RGL-treated group lowered the blood glucose and HbA1c levels by 19.6% and 11.4% compared to those in diabetic control group. In addition, plasma adiponectin and leptin levels in RGL-treated groups were increased by 20% and 12%, respectively, compared to those in diabetic control. Morphological analyses of liver, pancreas and epidydimal adipose tissue were done by hematoxylin-eosin staining, and pancreatic islet insulin and glucagon levels were detected by double-immunofluorescence staining. RGL-treated group revealed higher insulin contents and lower glucagon contents compared to diabetic control. To elucidate an action mechanism of Korean red ginseng, DNA microarray analyses were performed in liver and fat tissues, and western blot and RT-PCR were conducted in liver for validation. According to hierarchical clustering and principal component analysis of gene expression Korean red ginseng treated groups were close to metformin treated group. In summary, Korean red ginseng lowered the blood glucose level through protecting destruction of islet cells and shifting glucose metabolism from hepatic glucose production to glucose utilization and improving insulin sensitivity through enhancing plasma adiponectin and leptin levels.

• YAKHAK HOEJI
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• v.49 no.4
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• pp.306-311
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• 2005

Semisulospira libertine (SL) has been used as a folk medicine for quenching a thirst, hepatic fever and inflammation in oriental countries. Although SL has been anecdotally ascertained to ameliorate the hepatic diseases, there are no sufficient experimental evidences. The purpose of this study was to examine the effect of Bitam-S, in which SL is a main component, on non-alcoholic fatty liver disease manifested in C57BL/6J ob/ob mice. At 6 week old, the ob/ob mice were randomly divided into four groups; control and three treatment groups. The control mice was to receive a regular diet, and the treatment groups were fed a regular diet with either 250mg/kg, 500mg/kg of Bitam-S (BS250 and BS500) or 300mg/kg of metformin (MT300) for a 8-week period. Bitam-S exerted beneficial effects on lipid homeostasis in ob/ob mice that are not necessarily due to its ability to decrease food intake but its specific effects on hepatic lipogenesis related genes (SREBP1a, FAS and SCD-1). The combined effects of Bitam-S to reduce body weight and lipogenic gene expressions, and reduce the deposition of triglyceride in the liver are indicative of a marked improvement in obesity-related non-alcoholic fatty liver disease. Taken together, Bitam-S has potential as a treatment agent for non-alcoholic fatty liver disease and deserves clinical trial in the near future.

• Food Science and Biotechnology
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• v.15 no.6
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• pp.851-855
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• 2006

Acarviosine-glucose (AcvGlc) is an ${\alpha}$-glucosidase inhibitor and has similar inhibitory activity to acarbose in vitro. We synthesized AcvGlc by treating acarbose with Bacillus stearothermophilus maltogenic amylase and fed C57BL/6J and db/db mice with diets containing purified AcvGlc and acarbose for 1 week. AcvGlc (50 and 100 mg/100 g diet) significantly reduced plasma glucose and triglyceride levels in db/db mice by 42 and 51 %, respectively (p<0.0001). The hypoglycemic and hypotriglyceridemic effects of AcvGlc were slightly, but significantly, greater than those seen with acarbose treatment (p<0.0001) in C57BL/6J mice. In an oral glucose tolerance test, glucose tolerance was significantly improved at all time points (p<0.01). The expression of two novel glucose transporters (GLUTs), GLUT10 and GLUT12, were examined by Western blot analysis. GLUT10 was markedly increased in the db/db livers. After AcvGlc treatment, the expression of hepatic GLUT10 was decreased whereas intestinal GLUT12 was significantly increased in both strains of mice. Our results show that AcvGlc improves plasma lipid and glucose metabolism slightly more than acarbose. Regulation of hepatic GLUT10 and intestinal GLUT12 may be important in controlling blood glucose levels.

• Food Science and Biotechnology
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• v.16 no.6
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• pp.910-917
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• 2007

The aim of this study is to determine the anti-obesity effects of genistein and exercise, separately and in combination, in mice. Fifty male C57BL/6J mice were divided into 5 treatment groups: normal diet (ND), high fat diet (HD), high fat diet with exercise (HD+Ex), high fat diet with 0.2% genistein (HD+G), high fat diet with 0.2% genistein, and exercise (HD+G+Ex). They were allowed free access to feed and water, and exercised mice engaged in swimming on a regular basis for 12 weeks. Genistein supplemented mice gained less weight, had lower energy intake, better lipid profiles, and lower leptin than the HD mice. Furthermore, when genistein was combined with exercise (HD+G+Ex) the effects were even greater. HD, HD+Ex, and HD+G mice exhibited increased hepatic CPT-1 mRNA expression. Therefore, genistein and exercise has anti-obesity effects, as shown by changes in body weight, fat accumulation, energy intake, and leptin levels.

• Journal of Ginseng Research
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• v.34 no.4
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• pp.369-375
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• 2010

This study evaluated the protective effects of ginseng leaf extract (GLE) against high fat-diet-induced hyperglycemia and hyperlipidemia, and explored the potential mechanism underlying these effects in C57BL/6J mice. The mice were randomly divided into four groups: normal control, high fat diet control (HFD), GLE-treated at 250 mg/kg, and GLE-treated at 500 mg/kg. To induce hyperglycemic and hyperlipidemic states, mice were fed a high fat diet for 6 weeks and then administered GLE once daily for 8 weeks. At the end of the treatment, we examined the effects of GLE on plasma glucose, lipid levels, and the expression of genes related to lipogenesis, lipolysis, and gluconeogenesis. Both GLE groups lowered levels of plasma glucose, insulin, triglycerides, total cholesterol, and non-esterified fatty acids when compared to those in HFD group. Histological analysis revealed significantly fewer lipid droplets in the livers of GLE-treated mice compared with HFD mice. To elucidate the mechanism, Western blots and RT-PCR were performed using liver tissue. Compared with HFD mice, GLE-treated mice showed higher levels of phosphorylation of AMP-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase, but no differences in the expression of lipogenic genes such as sterol regulatory element-binding protein 1a, fatty acid synthase, sterol-CoA desaturase 1 and glycerol-3-phosphate acyltransferase. However, the expression levels of lipolysis and fatty acid uptake genes such as peroxisome proliferator-activated receptor-$\alpha$ and CD36 were increased. In addition, phosphoenolpyruvate carboxykinase gene expression was decreased. These results suggest that GLE ameliorates hyperglycemia and hyperlipidemia by inhibiting gluconeogenesis and stimulating lipolysis, respectively, via AMPK activation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.7
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• pp.1036-1042
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• 2013

The aim of the present study is to elucidate the anti-obesity effects of Doenjang with and without salt in C57BL/6J mice. For the analysis, a total of forty mice were randomly divided into four groups: normal diet group (ND), high-fat diet group (HD), high-fat diet supplemented with 20% Doenjang group (DJ), high-fat diet supplemented with 20% unsalted Doenjang group (NS). During the study period, food intake and body weight were measured daily and weekly, respectively. The animals were sacrificed after 12 weeks. Body weight gain, epididymal fat pad weight and serum triglyceride levels of DJ group were found to be significantly lower than those of the HD and NS groups. Serum total-cholesterol levels of DJ and NS groups were significantly lower as compared to the HD group. There were significant decreases in plasma insulin and leptin levels in DJ group compared with the HD and NS groups. We did not observe any significant changes in the expression of hepatic lipogenic-related gene $PPAR{\gamma}$ among the HD, DJ and NS groups. However, ACC expression was found to be significantly decreased in DJ group. Lipolysis-related gene ($PPAR{\alpha}$ and CPT-1) expression was significantly higher in the DJ group as compared to HD and NS groups. In conclusion, the results of this study showed that Doenjang supplementation lowers body weight gain and improves obesity-related parameters.

• Journal of Food Hygiene and Safety
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• v.24 no.4
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• pp.391-397
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• 2009

Carnosine is a dipeptide ($\beta$-alanyl-L-histidine) found in mammalian brain, eye, olfactory bulb and skeletal muscle at high concentrations. Its biological functions include antioxidant and anti-glycation activities. The objectives of this study were to investigate anti-diabetic effects of carnosine as determined by blood glucose levels in glucose tolerance test (GTT) and insulin tolerance test (ITT), insulin level and serum biochemical and lipid levels in male C57BL/6J db/db mice. There were five experimental groups including normal (C57BL/6J), control (vehicle), and three groups of carnosine at doses of 6, 30, and 150 mg/kg b.w. Carnosine was orally administered to the diabetic mice everyday for 8 weeks. There was no significant difference in body weight changes in carnosine-treated groups compared to the control. The treatments of carnosine significantly decreased the blood glucose level in the diabetic mice compared with the control (p < 0.05) after 5 weeks. The treatments of carnosine also significantly decreased the blood glucose levels in GTT and ITT and glycosylated hemoglobin (HbA1c), compared with the control (p < 0.05). Carnosine at the dose of 6 mg/kg significantly decreased the serum insulin level compared to the control (p < 0.05). Carnosine significantly increased total proteins but significantly decreased lactate dehydrogenase and blood urea nitrogen compared with the control (p < 0.05). Carnosine also significantly decreased glucose, LDL, and triglyceride in the serum of diabetic mice compared to the control (p < 0.05). These results suggest that carnosine has a hypoglycermic effect resulting from reduction of glucose and lipid levels and that high carnosine-containing diets or drugs may give a benefit for controlling diabetes mellitus in humans.

• Biomedical Science Letters
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• v.16 no.3
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• pp.151-159
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• 2010

The peroxisome proliferator-activated receptor $\alpha$ (PPAR$\alpha$) is a nuclear transcription factor that plays a central role in lipid metabolism and obesity. Exercise also is a powerful modifier of the manifestations of the lipid metabolism and obesity in animal models and humans with obesity and metabolic syndrome. However, effects of exercise on lipid metabolism and obesity in normal-weight younger female subjects, having functional ovaries and not metabolic disease, remain unexplained. To explore the effects of exercise on the development of obesity and its molecular mechanism in high fat diet-fed female C57BL/6J mice, we experimented the effects of swim training on body weight, adipose tissue mass, serum lipid levels, morphological changes of adipocytes and the expression of PPAR$\alpha$ target genes involved in fat oxidation in skeletal muscle tissue of female C57BL/6J mice. Swim-trained mice had significantly decreased body weight, adipose tissue mass, serum triglycerides compared with female control mice. Histological studies showed that swim training significantly decreased the average size of adipoctyes in parametrial adipose tissue. Swim training did not affect the expression of PPAR$\alpha$ mRNA in skeletal muscle. Concomitantly, swim training did not increase mRNA levels of PPAR$\alpha$ target genes responsible for fatty acid $\beta$-oxidation, such as carnitine palmitoyltransferase 1, medium chain acyl-CoA dehydrogenase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase, and thiolase in skeletal muscle. In conclusion, these results indicate that swim training regulates lipid metabolism and obesity in high fat diet fed-female mice although swim training did not increase mRNA levels of PPAR$\alpha$ target genes involved in fatty acid $\beta$-oxidation in skeletal muscle, suggesting that swim training may prevent obesity and improve fitness through other mechanisms in female with ovaries, not through the activation of skeletal muscle PPAR$\alpha$.