• 한방비만학회지
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• 제6권2호
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• pp.59-73
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• 2006

Objectives: This study was conducted to investigate the effects of Uncoupling protein (UCP) polymorphisms on weight loss. We analyzed associations between polymorphisms of UCP-2, 3 and changes in percentage of obesity phenotypes (Body mass index and percent body fat) after treatment. Materials and Methods: A total of 207 Korean women (BMI over 25) were recruited from the obesity clinic in Kirin Oriental Medical Hospital (Seoul, Korea). All patients were treated with a very low calorie diet and oriental medical therapy for one month. The effect of UCP polymorphisms on changes in obesity-phenotypes were analyzed. For the genotyping of a single nucleotide polymorphism (SNPs), genomic DNA from each subject was extracted from whole blood and genotyped using the TaqMan Method. Associations between changes in percentage of obesity phenotypes (BMI and percent body fat) and UCP polymorphisms were analyzed using age-adjusted general linear model. Results and Conclusions: In this study, AG, GG type of UCP-2 -866A>G, CC, CT type of UCP-2 +4787C>T, CG, GG type of UCP-3 +2564C>G, AG, GG type of UCP-3 +3106A>G, and TC, CC type of UCP-3 +4589T>C played a role as a resistance gene to weight loss.

• 식품과학과 산업
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• 제53권4호
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• pp.390-396
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• 2020

In vitro 및 동물시험 결과를 통해, 국내 천연 해양자원인 우뭇가사리 추출물의 체지방 감소 기능에 대해 살펴본 결과, 우뭇가사리 추출물이 고지방 식이 동물시험에서 체중 및 체지방 증가 억제 기능이 있음을 확인하였다. 우뭇가사리 추출물은 C/EBPα, β, SREPB-1, PPARγ 등 지방세포 분화 촉진 인자들의 발현을 억제하였고, 지방세포 분화 억제 조절 인자로 알려진 CHOP10의 발현은 촉진시켰다. 또한, 우뭇가사리 추출물은 AGTL의 발현을 촉진함으로써 지방분해 촉진 효과를 나타내었고, 중성지방의 합성 과정에 관여하는 LPAATθ, Lipin1, DGAT1 및 FAS의 발현을 억제하였으며, 지방 및 에너지 대사의 주요 조절 인자인 AMPK phosphorylation, PRDM16 및 UCP-1의 발현을 촉진하였다. 따라서 우뭇가사리 추출물은 체내 지방 대사에 있어서, 지방 합성 및 지방세포 분화를 억제하고, 지방분해 및 에너지 대사를 촉진하는 작용기전으로 체지방 감소 기능을 갖는 것으로 사료된다. 이러한 결과로 볼 때, 국내 천연 해양 자원인 우뭇가사리 추출물은 체내 지방 대사에 있어서 다양한 작용기전을 통해 우수한 체지방 감소 기능을 나타내고 있어 체지방 감소 건강기능식품 분야에서 유용한 신소재로 이용될 수 있을 것으로 생각된다. 나아가 본 연구진은 동물 시험에서 우뭇가사리 추출물의 혈당 조절 및 인슐린 저항성 개선 효과도 확인한 바 있어 대사증후군의 근본 원인인 복부 지방 및 인슐린 저항성 개선 효과를 모두 기대할 수 있는 소재로서의 가능성이 확인되었다. 추후 지질 및 당 대사에 관련된 작용기전 및 생체 지표의 상호 연관성, 인체에서의 혈당 개선 및 대사증후군 개선 효과 확인 등 추가 연구가 필요할 것으로 사료된다. 이를 통해 체지방 감소는 물론, 대사증후군 감소를 위한 건강기능식품 및 당뇨병 환자식 등의 분야에서 유용하게 이용될 수 있을 것으로 기대된다.

• Animal cells and systems
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• 제2권2호
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• pp.249-258
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• 1998

Obesity, one of the most common metabolic diseases in industrial countries is characterized by an increase in the number or size of adipocytes. In an effort to create transgenic mouse models for the study of obesity we developed a novel technique in which adipose tissue can be ablated genetically at will, at any specific developmental stage and/or physiological condition, by the treatment of ganciclovir. We made a series of adipocytespecific expression vectors using minimal regulatory regions of brown adipocyte-specific uncoupling protein (UCP-1) gene and adipocyte-specific aP2 gene, and then analyzed their expression characteristics in cultured cell lines. When both constructs pUCP-LacZ and paP2-LacZ were transfected transiently into differentiating 3T3-L1 (pre-while adipocytes) and HIB-1B (pre-brown adipocytes) cell lines in vitro and then monitored by X-gal staining of cells, these regulatory regions were sufficient to show proper differentiation stage-specific expression in adipocvtes. To confirm that adipocytes expressing HSV-TK controlled by these minimal requlatory elements are sufficient to kill themselves with ganciclovir treatment pUCP-TK and paP2-TK expression constructs were transfected stably into HIB-1B and 3T3-L1 cells, respectively, and their ganciclovir sensitivities were tested during in vitro differentiation of cells. As expected more than 80% of cells were dead by the 7th day of treatment with ganciclovir while negative control cells were not affected at all. The data suqqest that the constructed vectors are suitable for obtaining novel obese transqenic models based on a conditional genetic tissue ablation method.

• Nutrition Research and Practice
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• 제13권1호
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• pp.3-10
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• 2019

BACKGROUND/OBJECTIVES: The $NAD^+$ precursor nicotinamide riboside (NR) is a type of vitamin $B_3$ found in cow's milk and yeast-containing food products such as beer. Recent studies suggested that NR prevents hearing loss, high-fat diet-induced obesity, Alzheimer's disease, and mitochondrial myopathy. The objective of this study was to investigate the effects of NR on inflammation and mitochondrial biogenesis in AML12 mouse hepatocytes. MATERIALS/METHODS: A subset of hepatocytes was treated with palmitic acid (PA; $250{\mu}M$) for 48 h to induce hepatocyte steatosis. The hepatocytes were treated with NR ($10{\mu}M$ and 10 mM) for 24 h with and without PA. The cell viability and the levels of sirtuins, inflammatory markers, and mitochondrial markers were analyzed. RESULTS: Cytotoxicity of NR was examined by PrestoBlue assay. Exposure to NR had no effect on cell viability or morphology. Gene expression of sirtuin 1 (Sirt1) and Sirt3 was significantly upregulated by NR in PA-treated hepatocytes. However, Sirt1 activities were increased in hepatocytes treated with low-dose NR. Hepatic pro-inflammatory markers including tumor necrosis factor-alpha and interleukin-6 were decreased in NR-treated cells. NR upregulated anti-inflammatory molecule adiponectin, and, tended to down-regulate hepatokine fetuin-A in PA-treated hepatocytes, suggesting its inverse regulation on these cytokines. NR increased levels of mitochondrial markers including peroxisome proliferator-activated receptor ${\gamma}$ coactivator-$1{\alpha}$, carnitine palmitoyltransferase 1, uncoupling protein 2, transcription factor A, mitochondrial and mitochondrial DNA in PA-treated hepatocytes. CONCLUSIONS: These data demonstrated that NR attenuated hepatic inflammation and increased levels of mitochondrial markers in hepatocytes.

• 한국식품영양과학회지
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• 제42권1호
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• pp.1-7
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• 2013

본 연구에서는 3T3-L1 전지방세포를 이용하여 발효 삼정환의 지방 분화 억제 효과를 확인하고자 하였다. 삼정환을 5가지 주요 유산균으로 각각 발효시킨 후, Oil Red O 염색법으로 지방세포 분화 억제 여부를 알아보고, 이의 기전을 알기 위해서 지방생성에 핵심적인 역할을 하는 transcription factor 및 지질 조절 효소의 유전자 발현량을 비교하여 보았다. Oil Red O 염색 분석에서는 Lactobacillus plantarum, Enterococcus faecium으로 발효한 삼정환에서 지방구 수의 감소를 확인할 수 있었다. 또한 transcription factor로 $C/EPB{\alpha}$, $PPAR{\gamma}$, UCP-2 및 콜레스테롤 조절과 관련된 효소인 HMG-CoA reductase의 4가지 유전자 발현 정도를 분석하였는데, 발효시키지 않은 삼정환의 경우 농도가 $100{\mu}L/mL$ 이상일 때 네 가지 항목에서 억제 효과를 나타냈으며, 발효시켰을 때는 유산균의 종류에 따라 효과 억제효과가 있었는데, Lactobacillus plantarum으로 발효한 삼정환이 효과가 가장 좋은 것으로 나타났다. Lactobacillus plantarum으로 발효한 삼정환은 동일 농도의 발효하지 않은 삼정환과 비교했을 때, Oil Red O 실험에서 염색된 지방구 수가 더욱 감소하였으며, $PPAR{\gamma}$, UCP-2, HMG-CoA reductase의 경우 농도가 $200{\mu}L/mL$일 때 각각 35%, 57%, 54%로 5가지 발효 삼정환 중 가장 높은 억제율을 나타내었다. 이에 지방분화 억제 효과를 가진 삼정환을 발효시키면 그 효과가 더욱 증가하는 것으로 나타났는데, 특히 Lactobacillus plantarum으로 발효한 삼정환은 $PPAR{\gamma}$, UCP-2, HMG-CoA reductase의 유전자 발현조절을 통해 지방 분화를 억제시키는 것으로 밝혀져 발효 삼정환은 항비만 혹은 항고지혈증 약물로 개발 가능성이 있는 것으로 사료된다.

• Journal of Microbiology and Biotechnology
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• 제14권4호
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• pp.796-804
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• 2004

We found previously that dietary high fat caused obesity, and levan supplementation to the regular diet reduced adiposity and serum lipids. In the present study, we examined the effects of levan [high-molecular-mass $\beta$-(2,6)-linked fructose polymer] supplement on the development of obesity and lipid metabolism in rats fed with high-fat diet. Thus, to determine whether the dietary levan may have the anti-obesity and hypolipidemic effects, 4-wk-old Sprague Dawley male rats were fed with high-fat diet for 6 wk to induce obesity, and subsequently fed with 0, 1, 5, or 10% levan supplemented high-fat diets (w/w) for another 4 wk. For the comparison, a normal control group was fed with AIN-76A diet. Supplementation with levan resulted in a significant reduction of high-fat-induced body weight gain, white fat (i.e., epididymal, visceral, and peritoneal fat) development, adipocyte hypertrophy, and the development of hyperinsulinemia and hyperlipidemia in a dose-dependent manner. Serum triglyceride and free fatty acid levels were greatly reduced by levan supplementation. Serum total cholesterol level was reduced, whereas the HDL cholesterol level was increased by dietary levan. The expression of uncoupling protein (UCP) was increased by dietary high fat, and was further induced by levan supplementation. The mRNA level of UCP1, 2, and 3 in brown adipose tissue (BAT) and UCP3 in skeletal muscle was upregulated in rats fed with dietary levan. In conclusion, upregulated UCP mRNA expression may contribute to suppression of development of obesity through increased energy expenditure. The present results suggest that levan supplementation to the diet is beneficial in suppressing diet-induced obesity and hyperlipidemia.

• Journal of Nutrition and Health
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• 제54권4호
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• pp.335-341
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• 2021

Purpose: Muscle mitochondria play a key role in regulating fatty acid and glucose metabolism. Dysfunction of muscle mitochondria is associated with metabolic diseases such as obesity and type 2 diabetes. Isorhamnetin (ISOR), also known as 3-O-methylquercetin, a quercetin metabolite, is a naturally occurring flavonoid in many plants. This study evaluated the effects of ISOR on the regulation of the mitochondrial function of C2C12 muscle cells. Methods: C2C12 muscle cells were differentiated for 5 days, and then treated in various concentrations of ISOR. Cytotoxicity was determined by assessing cell viability using the water-soluble tetrazolium salt-8 assay principle at different concentrations of ISOR and time points. Levels of the mitochondrial DNA (mtDNA) content and gene expression were measured by quantitative real-time polymerase chain reaction. The citrate synthase (CS) activity was quantified by the enzymatic method. Results: ISOR at a concentration of 10 µM did not show any cytotoxic effects. ISOR increased the mtDNA copy number in a time- or dose-dependent manner. The messenger RNA levels of genes involved in mitochondrial function, such as peroxisome proliferator-activated receptor-γ coactivator-1α, and uncoupling protein 3 were significantly stimulated by the ISOR treatment. The CS activity was also significantly increased in a time- or dose-dependent manner. Conclusion: These results suggest that ISOR enhances the regulation of mitochondrial function, which was at least partially mediated via the stimulation of the mtDNA replication, mitochondrial gene expression, and CS activity in C2C12 muscle cells. Therefore, ISOR may be useful as a potential food ingredient to prevent metabolic diseases-associated muscle mitochondrial dysfunction.

• 한방재활의학과학회지
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• 제32권2호
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• pp.19-36
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• 2022

Objectives This study is to investigate the effects and mechanisms of Imyo-san (IMS) on the obese mice model induced by high-fat diet. Methods Antioxidative capacity was measured by in vitro method. C57BL/6 mice were randomly assigned into 5 groups (n=7). Normal group was fed general diet (Normal). The other 4 groups were fed high fat diet (HFD) with water (Control), with Garcinia gummi-gutta (GG, Garcinia gummi-gutta 200 mg/kg), with low-dose IMS (IMSL, Imyo-san 0.54 g/kg) and with high-dose IMS (IMSH, Imyo-san 1.08 g/kg). Results IMS showed high radical scavenging activity. After 6 week experiment, body weight, food intake, food efficiency ratio (FER), epididymal fat and liver weight, triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, sterol regulatory element-binding protein-1 (SREBP-1), phospho-acetyl-CoA carboxylase (p-ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), SREBP-2, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), phospho-liver kinase B1 (p-LKB1), phospho-AMP-activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor 𝛼 (PPAR𝛼), peroxisome proliferator-activated receptor 𝛾 coactivator-1𝛼 (PGC-1𝛼), uncoupling protein-2 (UCP-2), carnitine palmitoyltransferase 1A (CPT-1A), and histology of liver and epididymal fat were measured and analysed. Body weight gain, FER, liver and epididymal fat weight of IMS groups were significantly decreased. There were significant improvements in blood lipids with less TG, TC, LDL-cholesterol, VLDL-cholesterol and more HDL-cholesterol. Proteins associated with lipid synthesis (SREBP-1, p-ACC, FAS, SCD-1) and cholesterol (SREBP-2, HMGCR) was improved. Factors regulating lipid synthesis and lipid catabolism (p-LKBI, p-AMPK, PPARα, PGC-1α, UCP-2, CPT-1A) were increased. In histological examinations, IMS group had smaller fat droplets than control group. All results increased depending on concentration. Conclusions It can be suggested that IMS has anti-obesity effects with improving lipid metabolism.

• Nutritional Sciences
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• 제5권4호
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• pp.221-227
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• 2002

The objective of this study was to examine the effects of a weight loss program on the degree of obesity and levels of resting energy expenditure (REE) in overweight subjects according to their mitochondrial uncoupling protein 2 (UCP 2) genotype. Twenty-three subjects with a body mass index (BMI) greater than 27 were recruited from the Obesity Clinic of the Kyung-Hee University Hospital during the period of December 2000 - August 2001. The subjects were genotyped for the exon 8 allele; 15 subjects were found to be of del/del genotype, 8 were del/ins, and none were of ins/ins genotype. No significant association was found between the different UCP 2 genotypes and the initial levels of weight, fat mass (FM), lean body mess (LBM), BMI, REE, and REE/LBM ratio. After 12 weeks of a weight loss program, body weight and FM were significantly decreased, while LBM, total body water (TBW), and REE were not changed, irrespective of UCP 2 genotype. Initial fasting plasma levels of albumin, glucose, triglyceride, lipoprotein cholesterol, insulin, free triiodo-thyronine (T3), free fatty acid (FFA), and leptin were not different according to the UCP 2 genotype; furthermore, these blood parameters were not changed after the 12-week weight loss program. However, plasma levels of leptin decreased in both the del/del and ins/del genotypes, from 18.7 ng/ml to 13.4 ng/ml (p<.05), and from 18.1 ng/ml to 13.9 ng/ml (p＜.05), respectively, after the weight loss program. In conclusion, this study found no significant association between the del/del or del/ins UCP 2 genotypes and differing levels of REE or differing degrees of obesity, either before or after a weight loss program. This study provided evidence that a well- managed weight loss program could maintain levels of REE, which plays an important role in the maintenance of energy balance.

• Journal of Microbiology and Biotechnology
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• 제15권4호
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• pp.823-830
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• 2005

This study was undertaken to evaluate the effect of bacteria-derived $\beta$-glucan fiber on serum lipids, adiposity and uncoupling protein (UCP) expression in rats. In order to induce obesity, Sprague-Dawley weanling male rats were allowed free access to AIN-76A diet until 4 weeks of age, and fed high-fat diet (beef tallow, $40\%$ of calories as fat) for 6 weeks until 10 weeks of age. Rats were then fed with $0\%$ thigh- fat control group), $1\%$, or $5\%$ bacterial ~-glucan supplemented high-fat diets (w/w) for another 6 weeks. For comparison, normal control group was fed with AIN-76 diet $11.7\%$ fat). Supplementation with bacterial $\beta$-glucan resulted in a significant reduction of high-fat-induced white fat (i.e., visceral and peritoneal fat) development, adipocyte hypertrophy, and development of hyperinsulinemia and hyperleptinemia. Serum triglyceride, total cholesterol, and free fatty acid levels were greatly reduced, but, HDL-cholesterol concentrations were increased by bacterial $\beta$-glucan supplementation. Serum leptin level was lower in the $\beta$-glucan groups than in the high-fat group. The expression of UCPs (UCP1, UCP2, and UCP3) in brown adipose tissue (BAT) were significantly increased by $5\%$ bacterial $\beta$-glucan-containing diet. This study suggests that the anti-obesity effect of $5\%$ bacterial $\beta$-glucan is attributed to upregulation of UCPs and inefficient energy utilization.