• Title/Summary/Keyword: Ob/Ob Mice

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Acanthopanax senticosus Reverses Fatty Liver Disease and Hyperglycemia in ob/ob Mice

  • Park, Sang-Hyun;Lee, Sang-Gil;Kang, Sung-Keel;Chung, Sung-Hyun
    • Archives of Pharmacal Research
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    • v.29 no.9
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    • pp.768-776
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    • 2006
  • Non-alcoholic fatty liver disease (NAFLD) is common in obesity. However, weight reduction alone does not prevent the progression of NAFLD to end-stage disease associated with the development of cirrhosis and liver disease. In a previous experiment, 50% ethanol extract of Acanthopanax senticosus stem bark (ASSB) was found to reduce body weight and insulin resistance in high fat diet-induced hyperglycemic and hyperlipidemic ICR mice. To evaluate the anti-steatosis action of ASSB, insulin-resistant ob/ob mice with fatty livers were treated with ASSB ethanol extract for an 8 week-period. ASSB ethanol extract reversed the hepatomegaly, as evident in reduction of % liver weight/body weight ratio. ASSB ethanol extract also specifically lowered circulating glucose and lipids, and enhanced insulin action in the liver. These changes culminated in inhibition of triglyceride synthesis in non-adipose tissues including liver and skeletal muscle. Gene expression studies confirmed reductions in glucose 6-phosphatase and lipogenic enzymes in the liver. These results demonstrate that ASSB ethanol extract is an effective treatment for insulin resistance and hepatic steatosis in ob/ob mice by decreasing hepatic lipid synthesis.

Effects of Cheonghyul-San on the Generation of Redox Status and on the Expression of NF-${\kappa}$B Dependent Proteins (청혈산(淸血散)이 Redox Status 및 NF-${\kappa}$B 의존성 단백질에 미치는 영향)

  • Oh, Jeong-Pyo;Jeong, Ji-Cheon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.2
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    • pp.464-472
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    • 2009
  • The aim of this study was to investigate the effects of Cheonghyul-san on the generation of peroxynitrite ($ONOO^-$), nitric oxide (NO) and superoxide anion radical ( ${\cdot}\;O_2^-$), and on the expression of NF-${\kappa}$B-dependent proinflammatory proteins in ob/ob mice. Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57BL/6J black mice) and control obese (ob/ob mice) groups have received the standard chow. The experimental groups were fed with a diet of chow supplemented with 7.5, 15 and 30 mg Cheonghyul-san per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein-2 (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blot was performed using anti-IKK-${\alpha}$, anti-phospho I${\kappa}$B-${\alpha}$, anti-NF-${\kappa}$B (p50, p65), anti-COX-2, anti-iNOS, anti-VCAM-1 antibodies, respectively. Cheonghyul-san prevented $H_2O_2$-induced cell death. Cheonghyul-san inhibited the generation of $ONOO^-$, NO and ${\cdot}\;O_2^-$ in the $H_2O_2$-treated LLC-$PK_1$ cells. The generation of $ONOO^-$, NO and ${\cdot}\;O_2^-$ were inhibited in the Cheonghyul-san-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas the ratio was improved in the Cheonghyul-san-administered groups. Cheonghyul-san inhibited the protein expression levels of phospho-I${\kappa}$B-${\alpha}$, IKK-${\alpha}$, NF-${\kappa}$B (p50, p65), COX-2, iNOS and VCAM-1 genes. These results suggest that Cheonghyul-san is an effective scavenger of $ONOO^-$, ${\cdot}\;O_2^-$ and NO, and has an inhibitory effect on the expression of NF-${\kappa}$B-dependent inflammatory genes in ob/ob mice. Therefore, Cheonghyul-san might be used as a potential therapeutic drug against the diabetes- and obesity-related proinflammatory diseases.

Inhibition of Type II Diabetes in ob/ob Mice and Enhancement of Mitochodrial Biogenesis in C2C12 Myotubes by Korean Mistletoe Extract (한국산 겨우살이 추출물(KME)의 2형 당뇨 억제 및 근육세포 미토콘드리아 생성 증가 효과)

  • Jung, Hoe-Yune;Yoo, Yung Choon;Kim, Inbo;Sung, Nak Yun;Choi, Ok-Byung;Choi, Bo-Hwa;Kim, Jong-Bae
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.3
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    • pp.324-330
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    • 2015
  • In this study, the anti-diabetic activity of a cold water extract of Korean mistletoe (KME) was investigated in C57BL/6J Lep ob (ob/ob) mice. Oral administration of KME (50 or 100 mg/kg/d) significantly inhibited the level of blood glucose of ob/ob mice after 5 days from the beginning of KME treatment. And the anti-diabetic effect of KME was stabilized 10 days after oral administration, showing a substantial reduction of blood glucose levels by more than 20% as compared with control mice. The results of oral glucose tolerance test (OGTT) revealed that oral administration of KME gave rise to a remarkable improvement in overall glucose response. Oral administration of KME in ob/ob diabetic mice also significantly reduced blood total cholesterol (TCHO) and triglyceride (TG) levels compared with the diabetic control mice. Moreover, in an in vitro experiment using C2C12 myotubes, treatment of KME prominently increased glucose uptake. Interestingly, KME significantly increased the expression of peroxisome proliferator-activated receptor gamma coactivator 1-${\alpha}$ ($PGC-1{\alpha}$), a head regulator of mitochondrial biogenesis and oxidative metabolism, and $PGC-1{\alpha}$-associated genes such as glucose transporter type 4 (GLUT4), estrogen-related receptor-${\alpha}$ ($ERR-{\alpha}$), nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TmfA) in C2C12 cells. These results suggest that KME has potential as a novel therapeutic agent for diabetes, and its anti-diabetic activity may be related to the regulation of mitochondrial biogenesis.

Hangbisan, Sulfur-based Oriental Medicine, Lowers the Blood Cholesterol Level of ob/ob Obese Mice (유전성 비만 마우스에 대한 항비산의 혈중 콜레스테롤 저하 효과)

  • Chae, Myoung-Hee;No, Jin-Gu;Jhon, Deok-Young
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.1
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    • pp.27-31
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    • 2007
  • Among oriental medicine, sulfur is known to generate heat in the human body. Since body warming reaction results in the consumption of energy source, the medicines containing sulfur could help in the weight loss of laboratory rats. This study was designed to determine the possible weight loss effects of Hangbisan, sulfur based oriental medicine, on ob/ob mice. The obese mice were fed with standard diet containing 10% (w/w) Hangbisan or 10% (w/w) cellulose during 12 weeks. Hangbisan affected the weight loss of obese mice as cellulose did during experimental periods, while also reducing the level of plasma total cholesterol. These results suggest that dietary Hangbisan improved the composition of blood profiles in obese mice, and therefore has potential as an anti-obesity ingredient in the application of oriental medicine compounds.

The effects of the novel IDPc inhibitor, DA-11004, on NADPH generation, insulin secretion, and glucose level in obese diabetic (ob/ ob) mice

  • Lee, In-Ki;Yell, Shin-Chang;Bup, Sohn-Jin;Young, Jeong-Mi;Son-Miwon;Jun, Bae-Cheol;Soo, Byun-Jong;Kim, Dong-Sung;Kim, Soon-Hae
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.132.2-133
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    • 2003
  • The biological effects of NADPH-dependent isocitrate dehydrogenase (IDPc) inhibitor, DA-11004, was investigated in obese diabetic (ob/ ob) mice. DA-11004, metformin, and oxalomalate were daily injected (ip) for 8 weeks and after completing an 8-week period of experiment, mice were sacrificed at 1 hr after the last drugs treatment to collect their blood, liver, and adipose tissues(epididymal and retroperitoneal fat). (omitted)

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Gangjihwan Reduces Body Weight Gain in a ob/ob Female Mice (Ob/Ob 비만마우스 모델에서 강지환(降脂丸)의 체중감량 효과)

  • Baek, Song Young;Lee, Hye Rim;Park, Ju Hye;Yoon, Michung;Yoon, Yoosik;Yang, Heejung;Choi, Yung Hyun;Shin, Soon Shik
    • Herbal Formula Science
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    • v.25 no.2
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    • pp.193-207
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    • 2017
  • Objectives : This study was designed to investigate anti-obesity effects of DF in a ob/ob mouse model. Methods : Fifteen-week-old ob/ob mice were divided into four groups: a normal lean group given a standard diet, an ob/ob control group given a standard diet, and DF(1) and DF(2) groups given a standard diet with DF(1) (300 mg/kg), and DF(2) (600 mg/kg), respectively. After 10 weeks of treatment, body weight gain, feeding efficiency ratio, blood lipid markers, fat weight and histology were examined. Results : Body weight gain and fat mass were significantly decreased in DF(1) and DF(2) groups compared with control. The extent of decreases was eminent in DF(2) group. Feeding efficiency ratio were significantly decreased in DF(2) group compared with control. Consistent with their effects on body weight gain and fat mass, circulating concentrations of LDL, total cholesterol, free fatty acid, and insulin were decreased in DF(2) group compared with control. The size of adipocytes were significantly decreased by DF(2) compared with control. Consistent with their effects on body weight gain, hepatic lipid accumulation and liver weights were reduced in DF compared with control. Conclusions : In conclusion, these results suggest that DF not only decrease feeding efficiency ratio, and blood anti-obesity biomarkers, but also reduce fat mass, contributing to the improvement of obesity. DF also inhibits hepatic lipid accumulation.

Effects of ice creams supplemented with soy isoflavones on diabetic biomarkers in type II model mice (콩 이소플라본 첨가 아이스크림이 제2형 당뇨모델 마우스의 당뇨 지표에 미치는 영향)

  • Yang, Sun Hee;Choi, Young Sun
    • Korean Journal of Human Ecology
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    • v.23 no.1
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    • pp.137-148
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    • 2014
  • The aim of this study was to determine whether the addition of soy isoflavones to dairy ice cream modifies diabetic biomarkers in the type 2 diabetic model mice. Forty male C57BL/6J-ob/ob mice were randomly divided into 4 groups and fed control diet (basal, 7% fat), MS diet (milk ice cream with sugar, 20% fat), MS-SI diet (MS ice cream with 0.01% soy isoflavones, 20% fat), or MF-SI diet (milk ice cream with 0.01% soy isoflavones, 5% fructooligosaccharide, 20% fat) for 12 weeks. Blood response area by glucose tolerance test, plasma levels of glucose, insulin, C-peptide, leptin, and blood $HbA_{1c}$ were not significantly different among all the groups. Concentrations of interleukin-6 and tumor necrosis factor-${\alpha}$ secreted from splenocytes induced by Concanavalin A were not significantly different among all the groups. In conclusion, soy isoflavones supplemented to ice cream did not alter diabetic biomarkers in diabetic type 2 model mice.

Molecular biologic mechanism of obesity by GGEx18 (경신강지환(輕身降脂丸)18의 분자생물학적인 비만조절 기전에 관한 연구)

  • Lee, Hee-Young;Yoon, Ki-Hyeon;Seo, Bu-Il;Park, Gyu-Ryeol;Yoon, Mi-Chung;Shen, Zhi-Bin;Cui, Hong-Hua;Shin, Soon-Shik
    • 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.