• The Korean Journal of Physiology and Pharmacology
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• v.14 no.2
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• pp.99-103
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• 2010

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous type 2 diabetes (T2D), develops hyperglycemic obesity with hyperinsulinemia and insulin resistance after the age of 25 weeks, similar to patients with noninsulin-dependent diabetes mellitus (DM). In the present study, we determined whether there are differences in the pattern of gene expression related to glucose and lipid metabolism between OLETF rats and their control counterparts, Long-Evans Tokushima (LETO) rats. The experiment was done using 35-week-old OLETF and LETO rats. At week 35 male OLETF rats showed overt T2D and increases in blood glucose, plasma insulin, plasma triglycerides (TG) and plasma total cholesterol (TC). Livers of diabetic OLETF and LETO rats also showed differences in expression of mRNA for glucose and lipid metabolism related genes. Among glucose metabolism related genes, GAPDH mRNA was significantly higher and FBPase and G6Pase mRNA were significantly lower in OLETF rats. For lipid metabolism related genes, HMGCR, SCD1 and HL mRNA were substantially higher in OLETF rats. These results indicate that gluconeogenesis in OLETF rats is lower and glycolysis is higher, which means that glucose metabolism might be compensated for by a lowering of the blood glucose level. However, lipid synthesis is increased in OLETF rats so diabetes may be aggravated. These differences between OLETF and LETO rats suggest mechanisms that could be targeted during the development of therapeutic agents for diabetes.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.3
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• pp.317-325
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• 2017

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in parallel with worldwide epidemic of obesity. Reactive oxygen species (ROS) contributes to the development and progression of NAFLD. Peroxisomes play an important role in fatty acid oxidation and ROS homeostasis, and catalase is an antioxidant exclusively expressed in peroxisome. The present study examined the role of endogenous catalase in early stage of NAFLD. 8-week-old male catalase knock-out (CKO) and age-matched C57BL/6J wild type (WT) mice were fed either a normal diet (ND: 18% of total calories from fat) or a high fat diet (HFD: 60% of total calories from fat) for 2 weeks. CKO mice gained body weight faster than WT mice at early period of HFD feeding. Plasma triglyceride and ALT, fasting plasma insulin, as well as liver lipid accumulation, inflammation (F4/80 staining), and oxidative stress (8-oxo-dG staining and nitrotyrosine level) were significantly increased in CKO but not in WT mice at 2 weeks of HFD feeding. While phosphorylation of Akt (Ser473) and $PGC1{\alpha}$ mRNA expression were decreased in both CKO and WT mice at HFD feeding, $GSK3{\beta}$ phosphorylation and Cox4-il mRNA expression in the liver were decreased only in CKO-HF mice. Taken together, the present data demonstrated that endogenous catalase exerted beneficial effects in protecting liver injury including lipid accumulation and inflammation through maintaining liver redox balance from the early stage of HFD-induced metabolic stress.

• Korean Journal of Exercise Nutrition
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• v.13 no.3
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• pp.179-184
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• 2009

The purpose of this study was to evaluate a exercise combined with nutritional education for improving metabolic risk factor and dietary intakes in obese middle aged women. 35 obese (body mass index of at least ≥ 25 kg/m² or %body fat ≥ 30%) middle aged women were recruited from public health center. For intervention participants, their height, weight, percentage of body fat, waist circumference, blood pressure, lipid profiles, insulin resistance index, and nutrition intakes were measured at before and after post the intervention. And change of the total energy intakes per week was measured during intervention. The subjects underwent a 12 weeks educational program including nutritional education one day per week and, aerobic exercise 3 days per week (walking). After 12 weeks exercise program combined with nutritional education, body weight (p=0.002), percentage of body fat (p<0.001), BMI (p<0.001), waist circumference (p<0.001), WHR (p=0.004), TC (p=0.004), AI (p=0.006), DBP (p=0.010), MAP (p=0.013), glucose (p=0.018), insulin (p=0.003), HOMA-IR (p<0.001) were significantly decreased and cardiorespiratory fitness was significantly (p<0.001) increased. And energy intake was significantly (p<0.001) decreased and nutritional intake and intake-style were improved through 12 weeks exercise program combined with nutritional education.

• Herbal Formula Science
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• v.25 no.4
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• pp.457-469
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• 2017

Obesity is one of the most serious health problem because it induced numerous metabolic syndrome and increases the incidence of various disease, including diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. In 3T3-L1 adipocytes, increases in reactive oxygens species (ROS) occur with lipid accumulation. NADPH oxidase, producing superoxide anion, may contribute to the development of obesity-associated insulin resistance and type 2 diabetes. In this study, we elucidated the effect of Chaenomeles sinensis koehne extract (CSE) against the development of obesity and the inhibition mechanisms in 3T3-L1 preadiocytes. CSE decreased triglyceride content and inhibited the expression of adipogenic transcription factors including peroxisome proliferator-activated receptor $(PPAR){\gamma}$, CCAT/enhancer binding protein $(C/EBP){\alpha}$ and sterol regulatory element-binding protein (SREBP-1). In addition, CSE highly increased antioxidant activity in a dose-dependent manner. CSE remarkably reduced intracellular ROS increase and NAD(P)H oxidase activity, NOX1, NOX4, Rac1 protein expression, and phosphorylation of p47phox and p67phox We also studied the effect of CSE on weight gain induced by high-fat diet. The oral treatment of CSE (500 mg/kg, body weight) in diet-induced obese (DIO) mice showed decrease in triglyceride and adipocyte size. Therefore, these results indicate that the effect of CSE on anti-obese effects, adipocyte differentiation and reducing triglyceride contents as well as adipocyte size in obese mice, may be associated with inhibition of NAD(P)H oxidase-induced ROS production and adipose transcription factors. These results showed the potential to inhibit the obesity by CSE treatment through controlling the activation of NAD(P)H oxidase in vitro and in vivo obese model.

• Journal of Life Science
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• v.32 no.6
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• pp.476-481
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• 2022

Ubiquitin signaling regulates virtually all aspects of eukaryotic biology and dynamic processes in which protein substrates are modified by ubiquitin. To regulate these processes, deubiquitinating enzymes (DUBs) cleave ubiquitin or ubiquitin-like proteins from these substrates. DUBs have been implicated in the pathogenesis of cancer, leading to the development of increasing numbers of small-molecule DUB inhibitors. On the other hand, recent studies have focused on the function of DUBs in metabolic diseases such as obesity, diabetes, and fatty liver diseases. DUBs play a positive or negative role in the progression and development of metabolic diseases. Their involvement in cell pathology and regulation of major transcription factors in metabolic syndrome has been examined in vitro and in animal and human biopsies. UCH, USP7, and USP19 were linked to adipocyte differentiation, body weight gain, and insulin resistance in genetic or diet-induced obesity. CYLD, USP4, and USP18 were found to be closely associated with fatty liver diseases. In addition, these liver diseases were accompanied by body weight change in certain cases. Collectively, in this review, we discuss the current understanding of DUBs in metabolic diseases with a particular focus on obesity. We also provide basic knowledge and regulatory mechanisms of DUBs and suggest these enzymes as therapeutic targets for metabolic diseases.

• Microbiology and Biotechnology Letters
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• v.50 no.1
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• pp.135-146
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• 2022

Obesity is closely associated with profound dyslipidemia, insulin resistance, and fatty liver disease. Recent reports have suggested that alterations in gut microbiota can be linked to diet-induced obesity. In this study, the anti-obesity effects of Weissella confusa WIKIM51 isolated from kimchi were investigated, as evidenced by: i) reduced lipid accumulation and downregulated adipogenesis-related genes in 3T3-L1 adipocytes; ii) suppressed gains in body weight and epididymal fat mass; iii) reduced serum lipid levels, for example, triglyceride and total cholesterol; iv) increased serum adiponectin levels and reduced serum leptin levels; v) downregulated lipogenesis and upregulated β-oxidation-related genes in the epididymal fat; and vi) altered microbial communities. The collective evidence indicate the potential value of W. confusa WIKIM51 as a functional food supplement for the prevention and amelioration of obesity.

• Journal of Korean Medicine for Obesity Research
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• v.20 no.2
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• pp.138-148
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• 2020

Objectives: The aim of this study is to evaluate the effects of Bangpungtongseong-san (Fangfengtongsheng-san, BTS) and Daesiho-tang (Dachaihu-tang, DST) on weight loss and improvement in lipid metabolism and glucose metabolism. Furthermore, we intend to develop a prediction model for drug effects through the analysis of the single nucleotide polymorphism (SNP), gut-microbiota, and the expression of immune-related biomarkers. Methods: This study is a single-center, randomized, double-blind, parallel-design clinical trial. One hundred twenty-eight participants will be assigned to the BTS group (n=64) and DST group (n=64). Both groups will be administered 4 g medication three times a day for up to 2 weeks. The primary outcomes is weight loss. The secondary outcomes include bioelectrical impedance analysis, waist circumstance, body mass index, total cholesterol, high-density lipoprotein, triglyceride, insulin resistance. The exploratory outcomes include 3-day dietary recall, food frequency questionnaire, quality of life questionnaire, gut microbiota analysis, immune biomarkers analysis, and SNP analysis. Assessment will be made at baseline and at week 4, 8, and 12. Conclusions: This protocol will be implemented by approval of the Institutional Review Board of Dongguk University. The results of this trial will provide a systematic evidence for the treatment of obesity and enable more precise herbal medicine prescriptions.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.2
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• pp.190-196
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• 2018

Obesity has been reported to be a cluster of risk factors in the pathological ecology, In particular, there is increasing evidence that inflammation-related factors are associated with diabetes. This study examined the relationship between the hs-CRP level and FBG, fructosamine, and $HbA_1c$ in 4,734 non-diabetic adults aged 20 years or older, who were approved by the National Health and Nutrition Survey in 2015. The results showed that the FBG, fructosamine, and $HbA_1c$ levels increased with increasing BMI; the hs-CRP levels were the highest in the obese group, and HOMA-IR, an index of insulin resistance, was also significantly higher in the obese group. The hs-CRP level was the highest in obese adults. The levels of FBG, fructosamine. and $HbA_1c$, which are involved in blood glucose control, increased with increasing hs-CRP level. The FBG, fructosamine, and $HbA_1c$ levels increased significantly with increasing hs-CRP level after adjusting for various related variables. These results suggest that the obesity-induced increase in hs-CRP is a risk factor for diabetes mellitus in non-diabetic adults. Therefore, proper dietary habits and regular exercise should prevent diabetes by preventing obesity in non-diabetic adults.

• Korean Journal of Community Nutrition
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• v.4 no.2
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• pp.186-193
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• 1999

Recent epidemiologic and clinical students have shown that plasma cholesterol and triglyceride levels are independent risk factors for coronary heart disease. However, there is not much data on the characteristics of anthropometry and lipid profiles of hypercholesterolemia patients with hypertiglyceridemia. In this study, 112 hypercholesterolemic subjects$(T.C{\ge}240mg/dl)$ were divided into two groups by their plasma triglyceride levels. We compared the anthropometric measurements and lipid profiles of the subjects between the two groups : the simples hypercholesterolemic group(SHC, TG<200mg/dl) and the combined hypercholesterolemic group$(CHC, TG{\ge}250mg/dl)$. The distribution of the subjects into the SHC and CHC groups was 36.6% and 47.3%, respectively. The frequency of the CHC patients decreased with age. The subjects in this group had higher weight, BMI, HWR, cricumferences of mid arm, waist, hip and thigh, and skinfold thicknesses of biceps and triceps than those of the SHC subjects. The difference of plasma total cholesterol level was mainly due to the difference of VLDL-C levels. These differences resulted in the CHC subjects having higher atherogenic indexes and T-C/HDL-C ratios than those of the SHC subjects. Also, the former had higher Apo-B and insulin levels than those the latter. However, blood pressure, fasting blood glucose and HDL-C levels were not significantly different between the two groups. These results suggest that hypercholesterolemic patients with hypertriglyceridemia have riskier lipid profiles for CHD than those of patients with normal triglyceridemia. They also indicate that CHC is closely associated with glucose resistance syndrome(obesity, hyperglycemia, hyperinsulinemia and hypertriglyceridemia), and more prevalent in young people.

• The Journal of Korean Medicine
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• v.26 no.1 s.61
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• pp.85-92
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• 2005

Objective: A number of candidate genes have been in implicated in the pathogenesis of obesity in humans. Tumor necrosis factor-alpha $(TNF-{\alpha})$ is expressed primarily in adipocytes, and elevated levels of this cytokine have been linked to obesity and insulin resistance. Recently, the A allele of a polymorphism at position 308 in the promoter region of $TNF-{\alpha}$ (G-308A) has been shown to increase transcription of the gene in adipocytes. Therefore, we designed this study to test whether obese and non-obese subjects differ in $TNF-{\alpha}$ genotype distribution, and how the genotypes affect anthropometric parameters, including degrees of body mass index (BMI). Methods : The study included 153 obese but otherwise healthy women ($BMI{\geq}kg/m^2$, range 25-54.7, age range 15-40 years) and 82 non-obese healthy women ($BMI, age range 15-40 years). Total fat mass and percent body fat were determined by dual-energy X-ray absorptiometry. Genomic DNA was extracted and used for Ncol restriction fragment length polymorphism (RFLP) based genotyping of $TNF-{\alpha}$. Results: No differences were observed for allelic and genotype frequencies between the obese ($BMI{\geq}25$) and non-obese women. Also, no association of TNF-(l polymorphism was observed with body mass index (BMI) for genotype in obese women. In addition, age, pertent body fat, BMI, and cholesterol levels did not differ by $TNF-{\alpha}$ genotype. However, waist-to­hip ratio (WHR) was significantly lower in subjects with $TNF-{\alpha}$ GA or AA genotype (0.94 0.07 vs. 0.920.03, P<0.005). Conclusion: These results suggest that $TNF-{\alpha}$ promoter polymorphism at position-308 is not a significant factor for BMI, but affects the WHR in obese healthy women from Koreans.