• Biomedical Science Letters
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• v.19 no.1
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• pp.17-24
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• 2013

Animals show a sexual dimorphism in metabolic responses. We investigated to verify whether the peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) agonist fenofibrate regulates obesity and skeletal muscle lipid metabolism with sexual dimorphism and to determine the changes in skeletal muscle expression of $PPAR{\alpha}$ target genes. After both sexes of C57BL/6J mice received a high fat diet with or without fenofibrate for 7 weeks, we examined the effects of fenofibrate on not only body weight, adipose tissue mass, and skeletal muscle lipid accumulation, but also the mRNA expression of $PPAR{\alpha}$-related genes in skeletal muscle. Male mice given a fenofibrate-supplemented high fat diet showed decreased body weight gain and adipose tissue mass compared with mice fed a high fat diet alone, whereas fenofibrate did not reduce them in high fat diet-fed female mice. Lipid accumulation in skeletal muscle was inhibited by fenofibrate in male mice, but not in female mice. Gene expression analysis revealed that fenofibrate increased the mRNA levels of $PPAR{\alpha}$ target enzymes only in male mice. Therefore, our results suggest that sex-dependence differences in obesity and intramuscular lipid levels under fenofibrate treatment could be due in part to the differences in skeletal muscle $PPAR{\alpha}$ activation between male and female mice.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.3
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• pp.542-547
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• 2008

In order to examine anti-inflammatory effect of Cinnamomi Ramulus (CR) alcohol extract on rheumatoid arthritis, the present study investigated the viability and TNF-${\alpha}$ production in Raw264.7 cells treated with CR and collagen induced arthritis in DBA/1J mice which were orally administered with CR prior to immunization. The results are as follows: CR extract at $20{\mu}g/ml$ inhibited the viability of Raw264.7 by 50%. CR at 15 and $20{\mu}g/ml$ showed a significant decrease in TNF-${\alpha}$ levels from Raw264.7 cells treated with LPS. CR administration decreased arthritic index in DBA/1J mice immunized with bovine collagen type II but it did not reach statistical significance. CR administration significantly decreased spleen weights obtained from mice in 6 weeks after immunization. CR administration significantly decreased serum anti-type II collagen antibody levels compared with control group. CR administration decreased serum IL-6 levels compared with control group but it did not reach statistical significance.

• Biomedical Science Letters
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• v.11 no.1
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• pp.1-8
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• 2005

Fibrates are a class of hypolipidemic agents whose effects are mediated by activation of a specific transcription factor called the peroxisome proliferator-activated receptor $\alpha\;(PPAR\alpha).\;PPAR\alpha$ regulates the pathways of lipid catabolism such as fatty acid oxidation and the triglyceride metabolism, resulting in the treatment of hyperlipidemia. The decreased levels of plasma triglycerides by fibrates are responsible for hypertrophy and hyperpalsia of adipose cells. To determine whether fenofibrate regulates adipogenesis in female C57BL/6J mice, we measured the effects of fenofibrate on not only body weight, adipose tissue mass and serum triglycerides, but also the histology of adipose tissue and the expression of adipocyte marker genes. Fenofibrate did not inhibit high fat diet-induced increases in body weight, adipose tissue mass and serum triglycerides. Furthermore, fenofibrate did not cause the changes in the size and number of adipocytes and the expression of adipocyte-specific genes such as leptin and $TNF\alpha$. Therefore, this study demonstrates that fenofibrate does not affect adipogenesis in female mice.

• Journal of Acupuncture Research
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• v.23 no.2
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• pp.1-19
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• 2006

Objectives : The aim of this study was to investigate the hypoglycemic and hypolipidemic activities and mechanisms of Acanthopanax senticosus (AS) herbal acupuncture. Methods : Anti-diabetic and anti-steatotic activity of the AS herbal acupuncture was investigated on C57BL/6J ob/ob mice. After random grouping at the age of 9 weeks, the herbal acupuncture groups were injected subcutaneously at the left and right Gansu (BL18) corresponding acupuncture points alternately on exactly the same time every day with 0.1ml of either 400 mg/kg or 800 mg/kg of AS (AS400 and AS800) for 8-week period. As a positive control, metformin was administrated at a dose of 300 mg/kg (MT300). Body weights were measured weekly, and on every other week blood was collected for blood glucose analysis. At the end of study, blood was also collected for determination of plasma insulin and lipid levels, after which they were killed and periepidydimal fat, liver, muscle, and pancreas were immediately removed. The removed tissues were instantly soaked in liquid nitrogen and stored at $-70^{\circ}C$ for morphological examination and mRNA analysis. Results : The AS herbal acupuncture significantly prevented weight gain on C57BL/6J ob/ob mice. The AS herbal acupuncture lowered blood glucose and improved glucose tolerance in C57BL/6J ob/ob mice. The increase of insulin response during the OGTT was inhibited by the AS herbal acupuncture. Insulin sensitivity of skeletal tissue was enhanced. Plasma lipid levels were significantly improved in the AS herbal acupuncture groups. The AS herbal acupuncture decreased hepatic lipogenesis and hepatic triglyceride production, and increased fatty acid (FA) transporter that involves in FA uptake. The AS herbal acupuncture inhibited the increase of liver mass by prevention of the accumulation of TG but did not inhibit weight gain of fat tissue on C57BL/6J ob/ob mice. Conclusion : In summary, we have demonstrated several unique properties of the AS herbal acupuncture in decreasing body weight, and reversing insulin resistance and hepatic steatosis in ob/ob mice. This AS herbal acupuncture acts as an insulin sensitizer and specifically decreases circulating glucose and lipids, and suppresses hepatic lipogenesis.

• Development and Reproduction
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• v.21 no.1
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• pp.35-46
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• 2017

The process of spontaneous abortion involves a complex mechanism with various cytokines, growth factors, and hormones during the pregnancy. However, the mechanism underlying spontaneous abortion by pro- and anti-inflammatory cytokines in the serum during the pregnancy is not fully understood. Therefore, the purpose of this study was to examine the relationship between the serum levels of pro- and anti-inflammatory cytokines and spontaneous abortion using the $CBA/j{\times}DBA/2$ mouse model. Serum levels of pro-inflammatory cytokines, such as $IFN-{\gamma}$, $IL-1{\alpha}$ and $TNF-{\alpha}$ were not increased in abortion model mice, but anti-inflammatory cytokines, such as IL-4, IL-13 and IL-1ra were decreased compared to normal pregnant mice. In addition, serum levels of chemokine, such as SDF-1, G-CSF, M-CSF, IL-16, KC and MCP-1 were decreased in abortion model mice compared to normal pregnant mice. However, the expression levels of nesfatin-1/NUCB2 mRNA and protein in the uteri of implantation sites were significantly higher in abortion model mice than normal pregnant mice. These results suggest that uterine nesfatin-1/NUCB2 expression may be down-regulated by inflammatory cytokines and chemokines in the serum of pregnant mice. Moreover, this study suggests the possibility that nesfatin-1/NUCB2 expressed in the implantation sites may be associated with the maintenance of pregnancy.

• 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$\alpha$.

• Archives of Pharmacal Research
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• v.27 no.1
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• pp.48-52
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• 2004

DA-11004 is a synthetic, potent NADP-dependent isocitrate dehydrogenase (IDPc) inhibitor where $IC_{50}$ for IDPc is 1.49 $\mu$M. The purpose of this study was to evaluate the effects of DA-11004 on the high fat high sucrose (HF)-induced obesity in male C57BL/6J mice. After completing a 8-week period of experimentation, the mice were sacrificed 1hr after the last DA-11004 treatment and their blood, liver, and adipose tissues (epididymal and retroperitoneal fat)were collected. There was a significant difference in the pattern of increasing body weight between the HF control and the DA-11004 group. In the DA-11004 (100 mg/kg) treated group the increase in body weight significantly declined and a content of epididymal fat and retroperitoneal fat was also significantly decreased as opposed to the HF control. DA-11004 (100 mg/kg) inhibited the IDPc activity, and thus, NADPH levels in plasma and the levels of free fatty acid (FFA) or glucose in plasma were less than the levels of the HF control group. In conclusion, DA-11004 inhibited the fatty acid synthesis in adipose tissues via IDPc inhibition, and it decreased the plasma glucose levels and FFA in HF diet-induced obesity of C57BL/6J mice.

• Korean Journal of Agricultural Science
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• v.41 no.1
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• pp.47-58
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• 2014

The effect of conjugated linoleic acid (CLA) isomers esterified in diacylglycerol (DAG)-rich oil on lipid metabolism was investigated. Since dietary DAG has been known to induce the regression of atherosclerosis, CLA-DAG and olive-DAG oils containing similar levels of DAG (51.4~54.2%) were synthesized from olive oil. Hyperlipidemic C57BL/6J mice were then fed high-fat high-cholesterol diets supplemented with these oils (5% each) for 7 wk. The CLA-DAG diet containing 2.1% CLA isomers (0.78% c9,t11-CLA; 1.18% t10,c12-CLA) remarkably increased the levels of total plasma cholesterol and glutamic oxaloacetic transaminase (GOT) along with hepatic cholesterol and triacylglycerol (TAG) contents. Furthermore, the CLA-DAG diet inhibited fat uptake into adipose tissue whereas fat deposition (especially in the liver) was increased, resulting in the development of fatty livers. Hepatic fatty acid composition in the CLA-DAG mice was different from that of the olive-DAG mice, showing higher ratios of C16:1/C16:0 and C18:1/C18:0 in the liver. The activity of hepatic acyl-CoA:cholesterol acyltransferase (ACAT) was higher in CLA-DAG mice while plasma lecithin:cholesterol acyltransferase (LCAT) activity and the ferric reducing ability of plasma (FRAP) were lower in CLA-DAG mice compared to the olive-DAG animals. Results of the present study suggest that CLA incorporation into DAG oil could induce atherosclerosis in mice.

• 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 Haehwa Medicine
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• v.17 no.2
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• pp.185-198
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• 2008

Wished to examine closely effect that Atopy cream-Jawoongo ointment (A-J) used to atopy dermatitis disease patient get in atopy eruption control experimentally. In this research A-J ointment as treatment result to a NC/Nga mouse by BMAC ointment, clinical skin severity score decreased remarkably than control group. Thus, NC/Nga mice suffered from dermatitis very similar to human AD with IgE hyperproduction. Specially, result that measure IgE and IgG1 level in serum decreased remarkably than control group.