• 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.

• Fisheries and Aquatic Sciences
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• v.27 no.2
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• pp.122-135
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• 2024

Obesity is a disease involving mechanisms of fat accumulation, low-grade inflammatory cytokine release, and mitochondrial dysfunction. The aim of the current study was to investigate the effects of abalone intestine extract on fat metabolism in 3T3-L1 adipocytes and high fat diet-induced zebrafish larvae. The total phenol content was highest in subcritical water extract at 210℃ (SW210) among hot water, ethanol, and subcritical water extracts of abalone intestine. In addition, SW210 of male abalone intestine (MASW210) most effectively controlled the lipid accumulation and expression of adipogenic or lipogenic regulators (PPAR-γ, C/EBPα, SREBP-1c, and FAS) in 3T3-L1 adipocytes. Likewise, in zebrafish larvae fed high fat, MASW210 significantly suppressed body weight, glucose levels, and lipid accumulation. The mRNA expression related to adipogenesis (PPAR-γ and C/EBPα), lipogenesis (SREBP-1c and FAS), inflammatory cytokines (TNF-α and IL-6), energy m/;.etabolism (AMPK, lepr, SIRT1, and adiponectin), and mitochondrial biogenesis (PGC-1α and CPT-1) were significantly regulated by treatment with MASW210. These results suggest that abalone intestine extract such as MASW210, are useful biomaterials for improving obesity and metabolic diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.32 no.6
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• pp.384-395
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• 2018

The aim of this study was to investigate whether a novel formulation of an herbal extracts has an inhibitory effect on obesity. To determine its anti-obesity effects, we performed anti-obesity-related experiments in vitro and in vivo. Thus, our present study was carried out to evaluate the anti-obesity effect of herbal extracts using a high fat diet (HFD)-induced obese mouse model and 3T3-L1 adipose cells. The effects of each herbal extracts on lipid accumulation in 3T3-L1 cells were examined using Oil Red O staining. Results showed that treatment with each herbal extracts at $10{\sim}100{\mu}g/ml$ had no effect on cell morphology and viability. Without evidence of toxicity, herbal extracts treatment decreased lipid accumulation compared with the untreated adipocytes controls as shown by the lower absorbance of Oil Red O stain. Futhermore, compared with control-differentiated mature adipocytes, each herbal extracts significantly inhibited lipid accumulation in mature 3T3-L1 adipocytes. In the HFD-fed obese mice, body weight, liver weight and white adipose tissue weights were significantly reduced by mixture of herbal extracts administration in mouse skin. Futhermore, we found that mixture of herbal extracts administration suppressed serum triglyceride (TG), and total cholesterol (TCHO) in HFD-induced obese mouse model. The mixture of herbal extracts of permeability was estimated by measuring the transepithelial electrical resistance (TEER) value in pig skin. The optimized formulations of herbal extracts (Test 3 formulation) showed skin permeation. However, test 1 formulation containing essential oil as enhancer showed maximum skin permeation. After confirming the enhanced skin permeability, in vivo studies were performed to assess whether skin irritation potential on the basis of a primary irritation index (PII) in rabbit skin. Reactions were scored for erythema/edema reactions at 24 h, 48 h and 72 h post-application. It was concluded that the test 1 formulation was not irritation (PII = 0). The present study suggests that the test 1 formulation might be of therapeutic interest with respect to the treatment of obesity.

• The Journal of Pediatrics of Korean Medicine
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• v.21 no.2
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• pp.153-167
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• 2007

Objetives This experimental study is designed to investigate the effects of kwakhyangjungkisangamibang extract on the changes of adipose tissues, serum insulin and leptin levels in rats induced by a high fat diet. The leptin has been proposed to be involved in the role of food intake and energy expenditure. Methods During the 8 weeks of experimental period, male Sprague-Dawley rats were fed on the 2 different diets: the normal diet AIN-76A and high fat(beef tallow) diet ad libitum, of which 40% of the calories intake was fat. 9 rats in the control and high fat diet group were killed for the baseline experiment at 4 weeks of age. The high fat diet group was divided into three groups: control group, experimental group I(high fat diet plus kwakhyangjungkisangamibang extract), and experimental group II(high fat diet plus mahuang). The body weight, hypodermal fat tissue, serum lipid profile, insulin and leptin levels were measured after the administration of the high fat diet and extract. Results 1. The body weight was decreased in experimental group II, but there was not a significance difference compared to the control group. 2. The peritoneal, visceral, and hypodermal adipose tissue was decreased in experimental group I, but there was not a significance difference compared to the control group. 3. The lipid profile was decreased in experimental group I, but not in group II. 4. The insulin concentration was increased in experimental group I and II, but there was not a significance difference compared to the control group. 5. The leptin level was increased significantly in experimental group I(p<0.05) and II(p<0.01) compared to the control group. Conclusion The results of this study indicate that kwakhyangjungkisangamibang has an effect on the regulation of obesity.

• Applied Biological Chemistry
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• v.50 no.4
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• pp.295-303
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• 2007

A preliminary diet experiment utilizing Jerusalem artichoke's inulin, lotus leaf powder, nettle powder and eucalyptus powder extract indicated that combining all four elements gave the most effective result. Therefore, a study was conducted to evaluate the effectiveness of combined diet for weight loss. In this study, Sprague-Dawley, male white rats about 200 g in weight was fed with high fat diet for 8 weeks in order to induce obesity followed by 4 week administration of combined diet to look into the effect of the diet. After a total of 12 weeks of feeding, factors relevant to weight, blood, and lipid metabolism by liver in the body were researched and histologic change was examined with optical microscope. In terms of weight change, both high fat diet group and regular diet group gained weight from high fat diet for 8 weeks compared to normal group. Then, for another 4 weeks, while normal group and high fat diet group kept gaining weight, combined diet group which was provided with high fat diet for 8 weeks, lost weight to the normal group level after 3 week administration of diet. However, after the 4th week of administration, the group weighted significantly less than the normal group and the efficiency of diet also significantly dropped. In the biochemical analysis of blood, total cholesterol, LDL-cholesterol, triglyceride, glucose, GOT, GPT, ${\gamma}-GTP$ and creatine showed significant increase in high fat diet group and there was no significant difference between diet group and normal group except for GPT, ${\gamma}-GTP$ and creatine. In the biochemical analysis of liver, there was significant increase in LDL-cholesterol, triglyceride of high fat diet group compared to normal group, while there was no significant difference in term of total cholesterol and HDL-cholesterol. Compared to normal group, diet group had higher HDL-cholesterol, while total cholesterol dropped significantly. There was no significant difference in terms of LDL-cholesterol and triglyceride. Besides, in high fat diet group, observation of histologic change in liver and change in ultrastructure showed volume increase of hepatic cell and severe fatty degeneration in hepatic cell around hepatic vein. However in diet group, like normal group, no pathological change was observed in terms of cytoplasm, nucleus and capillary in hepatocyte and the alignment of hepatocyte had regularity thanks to the administration of combined diet. Therefore, combined diet utilizing Jerusalem artichoke's inulin, lotus leaf powder, nettle powder and eucalyptus powder was proven to be an effective measure to prevent and improve obesity as a result of abnormal adipose deposition.

• Toxicological Research
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• v.34 no.1
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• pp.41-48
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• 2018

The efficacy of highly active antiretroviral therapy (HAART) has led to an increase demand for therapeutic use, thereby necessitating investigation into drug toxicity. This study was designed to investigate the in vivo effects of HAART on sperm parameters and testicular oxidative stress in lean and obese rats. Wistar rats (males, n = 40, weighing 180~200 g) were assigned randomly into 4 groups and treated accordingly for 16 weeks as follows: Control (C): lean group fed with standard rat chow; Diet induced obesity (DIO): obese animals fed a high caloric diet; C + ART: lean animals treated with HAART; DIO + ART: obese animals treated with HAART. An antiretroviral drug combination of Tenofovir, Emtricitabine and Efavirenz at a dose of 17, 26 and 50 mg/kg/day was administered for the latter 6 weeks via jelly cube feeding. At the end of the experimental period, sperm analysis was performed on sperm collected from the caudal epididymis, while the testis was homogenized for antioxidant enzyme and lipid peroxidation assays. Results showed that HAART significantly decreased sperm motility (p < 0.05) in both lean and obese animals, and viability (p < 0.05) in the DIO group. Testicular glutathione, catalase and superoxide dismutase were significantly decreased (p < 0.05), while Thiobarbituric acid reactive substances (TBARS) levels were significantly increased (p < 0.05) when the DIO+ART group was compared to Control group. Thus, the decreased sperm qualities associated with HAART might be as a result of increased testicular oxidative stress prominent in obese animals.

• Molecules and Cells
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• v.38 no.12
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• pp.1037-1043
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• 2015

The TAZ activator 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2'-(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine] (TM-25659) inhibits adipocyte differentiation by interacting with peroxisome proliferator-activated receptor gamma. 1 TM-25659 was previously shown to decrease weight gain in a high fat (HF) diet-induced obesity (DIO) mouse model. However, the fundamental mechanisms underlying the effects of TM-25659 remain unknown. Therefore, we investigated the effects of TM-25659 on skeletal muscle functions in C2 myotubes and C57BL/6J mice. We studied the molecular mechanisms underlying the contribution of TM-25659 to palmitate (PA)-induced insulin resistance in C2 myotubes. TM-25659 improved PA-induced insulin resistance and inflammation in C2 myotubes. In addition, TM-25659 increased FGF21 mRNA expression, protein levels, and FGF21 secretion in C2 myotubes via activation of GCN2 pathways (GCN2-$phosphoelF2{\alpha}$-ATF4 and FGF21). This beneficial effect of TM-25659 was diminished by FGF21 siRNA. C57BL/6J mice were fed a HF diet for 30 weeks. The HF-diet group was randomly divided into two groups for the next 14 days: the HF-diet and HF-diet + TM-25659 groups. The HF diet + TM-25659-treated mice showed improvements in their fasting blood glucose levels, insulin sensitivity, insulin-stimulated Akt phosphorylation, and inflammation, but neither body weight nor food intake was affected. The HF diet + TM-25659-treated mice also exhibited increased expression of both FGF21 mRNA and protein. These data indicate that TM-25659 may be beneficial for treating insulin resistance by inducing FGF21 in models of PA-induced insulin resistance and HF diet-induced insulin resistance.

• IMMUNE NETWORK
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• v.22 no.2
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• pp.19.1-19.20
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• 2022

Coxsackievirus B3 (CVB3) infection causes acute pancreatitis and myocarditis. However, its pathophysiological mechanism is unclear. Here, we investigated how lipid metabolism is associated with exacerbation of CVB3 pathology using high-fat diet (HFD)-induced obese mice. Mice were intraperitoneally inoculated with 1×10⁶ pfu/mouse of CVB3 after being fed a control or HFD to induce obesity. Mice were treated with mitoquinone (MitoQ) to reduce the level of mitochondrial ROS (mtROS). In obese mice, lipotoxicity of white adipose tissue-induced inflammation caused increased replication of CVB3 and mortality. The coxsackievirus adenovirus receptor increased under obese conditions, facilitating CVB3 replication in vitro. However, lipid-treated cells with receptor-specific inhibitors did not reduce CVB3 replication. In addition, lipid treatment increased mitochondria-derived vesicle formation and the number of multivesicular bodies. Alternatively, we found that inhibition of lipid-induced mtROS decreased viral replication. Notably, HFD-fed mice were more susceptible to CVB3-induced mortality in association with increased levels of CVB3 replication in adipose tissue, which was ameliorated by administration of the mtROS inhibitor, MitoQ. These results suggest that mtROS inhibitors can be used as potential treatments for CVB3 infection.

• Journal of Acupuncture Research
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• v.25 no.2
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• pp.259-266
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• 2008

Objectives : To learn the effects of $CV_{12}\;{\cdot}\;CV_9$ and $LI_4\;{\cdot}\;LI_{11}$ electroacupuncture stimulation on high fat diet induced-obese mouse. Methods : The control group was provided with high fat diet without electroacupuncture stimulation, while the experimental group $CV_{12}\;{\cdot}\;CV_9$ and $LI_4\;{\cdot}\;LI_{11}$ with three frequencies(10Hz, 100Hz, 200Hz) for 5 times a week during five week periods with the high fat diet. We investigated the body weight, weight gain, and food intake. Results : After the electroacupuncture stimulation, a significant loss of increasement in weight was found in the experimental group compared with the high fat diet group. But there was no significant difference made by the change of acupoint combinations and frequencies. After the electroacupuncture stimulation, no significant change was found in the food intakes, but the weight gain a week was decreased compared with high fat diet group. Conclusions : These results suggest that electroacupuncture stimulation on $CV_{12}\;{\cdot}\;CV_9$ and $LI_4\;{\cdot}\;LI_{11}$ might be effective in treatments of obesity to high fat diet.

• Korean Journal of Acupuncture
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• v.36 no.4
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• pp.274-280
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• 2019

Objectives : This preliminary study investigated the effect of acupuncture treatment on short-term ketogenic diet-induced weight loss and glucose intolerance in mice. Methods : Six-week old male C57BL/6J mice were randomly assigned to 3 groups: normal, KD, and KD+ACU. All the mice except normal group were fed with ketogenic diet formula for 7 weeks and mice in KD+ACU group received acupuncture treatment three times a week. Body weights were measured three times a week, and glucose level was measured on week 1,3,5, and 7. Ketone level was measured on week 3,5, and 7. Results : Ketogenic diet showed short-term weight loss effect, however, acupuncture treatment did not affect on the weight loss. Ketone level was increased in KD fed mice compared to normal diet fed mice and the level was decreased in KD+ACU group on week 3. However, the change was not significantly different compared to KD group on week 7. Glucose intolerance was improved in KD+ACU group compared to KD group. Conclusions : Acupuncture treatment was effective in relieving glucose intolerance, and the results suggest that combining acupuncture treatment with ketogenic diet may complement each therapeutic intervention by improving glucose intolerance but not effecting on weight loss. This study provides meaningful evidence as a preliminary study of acupuncture treatment on ketogenic diet.