• Journal of Ginseng Research
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• v.41 no.1
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• pp.23-30
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• 2017

Background: Ginsenoside Rg1 is a class of steroid glycoside and triterpene saponin in Panax ginseng. Many studies suggest that Rg1 suppresses adipocyte differentiation in 3T3-L1. However, the detail molecular mechanism of Rg1 on adipogenesis in 3T3-L1 is still not fully understood. Methods: 3T3-L1 preadipocyte was used to evaluate the effect of Rg1 on adipocyte development in the differentiation in a stage-dependent manner in vitro. Oil Red O staining and Nile red staining were conducted to measure intracellular lipid accumulation and superoxide production, respectively. We analyzed the protein expression using Western blot in vitro. The zebrafish model was used to investigate whether Rg1 suppresses the early stage of fat accumulation in vivo. Results: Rg1 decreased lipid accumulation in early-stage differentiation of 3T3-L1 compared with intermediate and later stages of adipocyte differentiation. Rg1 dramatically increased CAAT/enhancer binding protein (C/EBP) homologous protein-10 (CHOP10) and subsequently reduced the $C/EBP{\beta}$ transcriptional activity that prohibited the initiation of adipogenic marker expression as well as triglyceride synthase. Rg1 decreased the expression of extracellular signal-regulated kinase 1/2 and glycogen synthase kinase $3{\beta}$, which are also essential for stimulating the expression of $CEBP{\beta}$. Rg1 also reduced reactive oxygen species production because of the downregulated protein level of nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase 4 (NOX4). While Rg1 increased the endogenous antioxidant enzymes, it also dramatically decreased the accumulation of lipid and triglyceride in high fat diet-induced obese zebrafish. Conclusion: We demonstrated that Rg1 suppresses early-stage differentiation via the activation of CHOP10 and attenuates fat accumulation in vivo. These results indicate that Rg1 might have the potential to reduce body fat accumulation in the early stage of obesity.

• Journal of Applied Biological Chemistry
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• v.64 no.4
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• pp.383-389
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• 2021

Obesity is associated with impaired intestinal epithelial barrier function, which contribute to host systemic inflammation and metabolic dysfunction. Korean traditional foods, fiber-rich bean products, have been various biological activities in anti-inflammatory responses, but has not reported the large intestinal health. In this study, we investigated the intestinal health promoting effect of cooked soybeans (CSB) on high fat diet (HFD)-induced obesity model. SD rat were fed either a HFD or HFD supplemented with 10.6% CSB (HFD+CSB) for animal experimental period. CSB treatment significantly decreased the HFD-induced weights of body and fat. Also, CSB treatment improved HFD-reduced tight junction components (ZO-1, Claudin-1, and Occludin-1) mRNA expression in large intestine tissue. Additionally, histopathological evaluation showed that CSB treatment attenuated the HFD-increased inflammatory cells infiltration and epithelial damages in large intestine tissue. At the genus level, effects of CSB supplement not yet clear, while dietary effects showed differential abundance of several genera including Lactobacillus, Duncaniella, and Alloprevotella. NMDS analysis showed significant microbial shifts by HFD, while CSB did not shift gut microbiota. CSB increased the abundance of the genera Anaerotignum, Enterococcus, Clostridium sensu stricto, and Escherichia/Shigella by linear discriminant analysis effect size analysis, while reduced the abundance of Longicatena and Ligilactobacillus. These findings indicate that CSB supplement improves HFD-deteriorated large intestinal health by the amelioration of tight junction component, while CSB did not shift gut microbiotas.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.5
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• pp.519-529
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• 2017

Sodium butyrate (SB) has various metabolic actions. However, its effect on dipeptidyl peptidase 4 (DPP-4) needs to be studied further. We aimed to evaluate the metabolic actions of SB, considering its physiologically relevant concentration. We evaluated the effect of SB on regulation of DPP-4 and its other metabolic actions, both in vitro (HepG2 cells and mouse mesangial cells) and in vivo (high fat diet [HFD]-induced obese mice). Ten-week HFD-induced obese C57BL/6J mice were subjected to SB treatment by adding SB to HFD which was maintained for an additional 16 weeks. In HepG2 cells, SB suppressed DPP-4 activity and expression at sub-molar concentrations, whereas it increased DPP-4 activity at a concentration of $1,000{\mu}M$. In HFD-induced obese mice, SB decreased blood glucose, serum levels of insulin and $IL-1{\beta}$, and DPP-4 activity, and suppressed the increase in body weight. On the contrary, various tissues including liver, kidney, and peripheral blood cells showed variable responses of DPP-4 to SB. Especially in the kidney, although DPP-4 activity was decreased by SB in HFD-induced obese mice, it caused an increase in mRNA expression of $TNF-{\alpha}$, IL-6, and $IL-1{\beta}$. The pro-inflammatory actions of SB in the kidney of HFD-induced obese mice were recapitulated by cultured mesangial cell experiments, in which SB stimulated the secretion of several cytokines from cells. Our results showed that SB has differential actions according to its treatment dose and the type of cells and tissues. Thus, further studies are required to evaluate its therapeutic relevance in metabolic diseases including diabetes and obesity.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.5
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• pp.335-344
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• 2019

Obesity causes inflammation and impairs thermogenic functions in brown adipose tissue (BAT). The adipokine lipocalin 2 (LCN2) has been implicated in inflammation and obesity. Herein, we investigated the protective effects of caloric restriction (CR) on LCN2-mediated inflammation and oxidative stress in the BAT of high-fat diet (HFD)-fed mice. Mice were fed a HFD for 20 weeks and then either continued on the HFD or subjected to CR for the next 12 weeks. CR led to the browning of the white fat-like phenotype in HFD-fed mice. Increased expressions of LCN2 and its receptor in the BAT of HFD-fed mice were significantly attenuated by CR. Additionally, HFD+CR-fed mice had fewer neutrophils and macrophages expressing LCN2 and iron-positive cells than HFD-fed mice. Further, oxidative stress and mitochondrial fission induced by a HFD were also significantly attenuated by CR. Our findings indicate that the protective effects of CR on inflammation and oxidative stress in the BAT of obese mice may be associated with regulation of LCN2.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.8
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• pp.1190-1197
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• 2017

Objective: Adipose tissue is no longer considered as an inert storage organ for lipid, but instead is thought to play an active role in regulating insulin effects via secretion adipokines. However, conflicting reports have emerged regarding the effects of adipokines. In this study, we investigated the role of adipokines in glucose metabolism and insulin sensitivity in obese Bama mini-pigs. Methods: An obesity model was established in Bama mini-pigs, by feeding with high-fat and high-sucrose diet for 30 weeks. Plasma glucose and blood biochemistry levels were measured, and intravenous glucose tolerance test was performed. Adipokines, including adiponectin, interleukin-6 (IL-6), resistin and tumor necrosis factor alpha ($TNF-{\alpha}$), and glucose-induced insulin secretion were also examined by radioimmunoassay. AMP-activated protein kinase (AMPK) phosphorylation in skeletal muscle, which is a useful insulin resistance marker, was examined by immunoblotting. Additionally, associations of AMPK phosphorylation with plasma adipokines and homeostasis model assessment of insulin resistance (HOMA-IR) index were assessed by Pearce's correlation analysis. Results: Obese pigs showed hyperglycemia, high triglycerides, and insulin resistance. Adiponectin levels were significantly decreased (p<0.05) and IL-6 amounts dramatically increased (p<0.05) in obese pigs both in serum and adipose tissue, corroborating data from obese mice and humans. However, circulating resistin and $TNF-{\alpha}$ showed no difference, while the values of $TNF-{\alpha}$ in adipose tissue were significantly higher in obese pigs, also in agreement with data from obese humans but not rodent models. Moreover, strong associations of skeletal muscle AMPK phosphorylation with plasma adiponectin and HOMA-IR index were obtained. Conclusion: AMPK impairment induced by adiponectin decrease mediates insulin resistance in high-fat and high-sucrose diet induction. In addition, Bama mini-pig has the possibility of a conformable model for human metabolic diseases.

• Journal of Life Science
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• v.25 no.12
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• pp.1432-1438
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• 2015

Although exercise training has been utilized to improve vascular function in animals and humans, the impact of moderate intensity exercise training on fibrinolytic activities and nitric oxide (NO) bioavailability has not been well documented. Therefore, the purpose of the current study was to examine the impact of moderate intensity aerobic exercise training on fat mass, blood lipid profiles, fibrinolytic activity, and NO levels in high-fat-diet induced rats. The body weight, fat mass, blood lipid profiles, fibrinolytic activity, and nitrite/nitrate were measured pre- and postexercise (10 weeks) training. The body weight and fat mass reduced significantly in the exercise (EX) group compared to the control (CON) group. Blood lipid profiles and low-density lipoprotein were unchanged in the EX group compared to the CON group. However, triglyceride and free fatty acid were significantly lower in the EX group compared to the CON group, and high-density lipoprotein was significantly greater in the EX group compared to the CON group. In addition, fibrinolytic activity and nitrite/nitrate were significantly greater in the EX compared to the CON group. These results suggest that 10 weeks of the moderated intensity aerobic exercise training improves blood lipid profiles, fibrinolytic activity, and the nitrite/nitrate ratio, which may improve vascular health and reduce obesity-related cardiovascular disease risks in high-fat- diet induced rats.

• Journal of Life Science
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• v.23 no.6
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• pp.779-788
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• 2013

This study was to investigate the effect of high-fat diet on macrophage immunocompetence in C57BL/6 mice. C57BL/6 male mice (4 weeks aged, n=16) were divided into two groups. HD groups fed high-fat diet (45% of fat) and ND groups fed chow diet (10% of fat). Peritoneal macrophages were obtained from each mouse intra-peritoneal by sterile lavage method. Macrophage were stimulated with $1{\mu}g/ml$ of lipopolysaccharide (LPS) for 24 hr. Body weight was significantly increased by high-fat diet. Macrophage phagocytosis of HD was significantly lower than that of ND. After 24 hr of LPS stimulation, NO, IL-$1{\beta}$ and IFN-${\gamma}$ production of HD were significantly lower than those of ND. There were no significant differences in the production of TNF-${\alpha}$ and IL-12 between HD and ND. These findings suggest that high fat diet-induced obesity is associated with decreased Immunocompetence and antigen-stimulated sensitivity of peritoneal macrophage, and lower production of NO, IL-$1{\beta}$ and IFN-${\gamma}$ may contribute to these changes.

• Journal of Acupuncture Research
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• v.21 no.2
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• pp.131-153
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• 2004

Objectives : This research was performed to investigate the effect of herbal acupuncture (Atratylodes japonica Koizumi and Coix lachrymajobi var. mayeun Stapf) at Pungnyung(ST40) and Umnungchon(SP9) on weight gain, food intake, food efficiency, serum of lipid concentrations, liver function and HDL to total cholesterol ratio of rats fed high fat diet for 5weeks. Methods : Experimental groups were divided into normal group(Sham), high fat diet group(Control), high fat diet and Atractylodes japonica-herbal acupuncture in ST40 SP9 treated group (AJ), high fat diet and Coix lachrymajobi var. mayeun Stapf-herbal acupuncture in ST40 SP9 treated group(CL), high fat diet and Atractylodes japonica+Coix lachrymajobi var. mayeun Stapf-herbal acupuncture in ST40 SP9 treated group(AJ+CL). Herbal acupuncture was bilaterally treated at the level of 132.5mg/kg body weight per day. Results : Body weight and food efficiency were decreased in AJ, AJ+CL. Feed intake was decreased in AJ, CL. The level of serum HDL-cholesterol was increased in AJ, CL. The level of serum total cholesterol, LDL-cholesterol and phospholipid were not significant. The level of serum triglyceride, free fatty acid were increased in AJ. The level of serum AST was decreased in AJ, AJ+CL. The level of serum ALT was decreased in AJ, CL, AJ+CL. The level of serum ALP was decreased in AJ+CL. The HDL to Total cholesterol ratio was increased in AJ. Conclusions : Atractylodes japonica-herbal acupuncture in ST40 SP9 can control the body weight, feed intake and feed efficiency ratio, HDL-cholesterol and herbal acupuncture combined Atractylodes japonica with Coix lachrymajobi var. mayeun Stapf is effective on Body weight, feed intake, feed efficiency ratio, protection of liver function and prevention cardiovascular risk by obesity.

• Food Science and Preservation
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• v.24 no.5
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• pp.666-672
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• 2017

The purpose of this study was to examine the effects of long-term endurance exercise and salvia miltiorrhiza vinegar on body composition and insulin resistance of high-fat diet (30% carbohydrate, 50% fat and 20% protein) induced obese rats. After 8 weeks of high fat diet (50% of total calories), rats were divided into 4 groups (sedentary group, n=10; exercise group, n=10; Salvia miltiorrhiza vinegar group, n=10; exercise+Salvia miltiorrhiza vinegar group, n=10) for 8 weeks. Body weight, body composition, diet intake volume, oral glucose tolerance test, plasma total cholesterol were measured. The results showed that Salvia miltiorrhiza vinegar plus endurance exercise training for 8 weeks significantly improved body weight control, visceral fat weight, and insulin resistance. However, only Salvia miltiorrhiza vinegar treatment did not significantly improve body composition and insulin resistance. In addition, there was no additive by the combination of Salvia miltiorrhiza vinegar and endurance exercise in insulin, body fat, and total cholesterol. The reduction of body fat, glucose, insulin and cholesterol by combination was resulted from the exercise. These results suggest that Salvia miltiorrhiza vinegar has slight effect on anti-hyperglycemia and anti-obesity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.9
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• pp.1235-1243
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• 2011

In this study, we investigated the antioxidative activity (scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical and superoxide anion radical) and anti-obesity effects of black bean chungkugjang extract (BBCE). DPPH free radical-scavenging activity and superoxide anion radical-scavenging activity ($SC_{50}$ value) of BBCE were $162.7{\pm}2.8$ ppm, and $205.62{\pm}3.6$ ppm, respectively. The anti-obesity effects of BBCE were investigated by measuring Oil Red O staining in 3T3-L1 adipocytes. BBCE reduced the content of Oil Red O dye in 3T3-L1 adipocytes. We also examined the effects of BBCE on adiposity, serum lipid, and leptin levels in obese mice fed a high-fat diet. Mice were fed the BBCE experimental diets for 7 weeks, after which they were sacrificed. ICR male mice were randomly divided into three groups, one normal diet group (ND group) and two high fat diet groups with or without BBCE supplementation (HFD group and HFD-BBCE group). The results showed that weight gain and the food efficiency ratio significantly decreased upon addition of BBCE compared to those of the HFD group. Further, white adipose tissue weights of epididymal, mesenteric, and retroperitoneal areas in the HFD-BBCE group were reduced to 34.8%, 7.1%, and 40.6%, respectively, compared to that of the HFD group. The serum levels of triglycerides, total cholesterol, LDL-cholesterol, and leptin in the HFD-BBCE group were significantly lower than those of the HFD group. Based on these results, it can be concluded that BBCE may have beneficial effects on reducing fat mass and serum lipid content.