• 생명과학회지
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• 제24권8호
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• pp.895-902
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• 2014

아디포넥틴은 이미 합성된 GLUT4의 translocation 증가를 통해 포도당의 세포내 유입을 촉진하며 인슐린 민감도를 증가시키는 것으로 알려져 있다. 본 연구에서는 장기간(6주령부터 16, 26, 36, 47, 및 77주령까지)의 고지방식이(HFD)를 섭취한 비만 C57BL/6 생쥐와, 칼로리제한(CR) 또는 thiazolidinedione (TZD) 섭취에 의해 인슐린 민감성이 회복된 생쥐들로부터 지방조직을 적출하여 아디포넥틴과 GLUT4 의 mRNA 발현의 변화를 조사하였으며, 선형회귀분석(linear regression analysis)을 통해 아디포넥틴과 GLUT4 유전자 발현량 사이의 상관관계를 평가하여 아디포넥틴이 GLUT4 유전자 발현의 전사단계에서도 영향을 미치는지의 가능성을 확인하고자 하였다. 지방조직에서의 유전자 발현량은 TaqMan probe를 이용한 real-time PCR로 정량되었다. 실험결과, 지방조직에서의 아디포넥틴 mRNA발현량은 여러 조건의 생쥐 그룹들 사이에 유의한 변화가 나타나지 않았지만, GLUT4의 유전자 발현량은 HFD군에서는 감소하고, CR군(p<0.05)과 TZD군(p=0.007)에서는 유의하게 증가하는 변화가 확인되었다. 또한, 아디포넥틴과 GLUT4 mRNA 발현량 사이에는 유의한 상관관계를 나타내고 있음이 확인되었다. ND군(p<0.0001), HFD군 p<0.0001), 또는 각각의 주령과 식이별 소그룹, 그리고 CR군(p=0.002) 에서도 두 유전자간의 발현량이 유의하게 연관되어 있었다. 그러나 TZD군(p=0.73)의 생쥐에서는 그 연관성이 사라짐을 관찰하였다. 이는 TZD가 아디포넥틴 유전자 발현에는 영향을 미치지 않지만, GLUT4유전자 발현은 촉진하기에 두 유전자 사이에 유의하지 않은 상관관계로 변화되었음을 시사한다. 이들 결과는 아디포넥틴과 GLUT4의 유전자 발현은 강하게 연관되어 있으며, 두 유전자 발현 조절에 대한 공통적인 작용기전의 존재 가능성 또는 아디포넥틴이 GLUT4 translocation뿐만 아니라 GLUT4의 유전자 발현에도 직접적으로 작용하고 있음을 시사한다.

• 생명과학회지
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• 제27권8호
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• pp.937-944
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• 2017

본 연구에서는 한천식이섬유(Diet fiber of agar)가 지방과 포도당대사에 미치는 효과를 연구하고자, 고지방사료(High fat diet, HFD)를 급여한 C57BL/6 마우스에 한천함유음료(beverage contained agar, BCA)를 9주 동안 투여하고 지방축적, 지질농도, 인슐린농도 등의 변화를 분석하였다. 식이섭취효율은 HFD+BCA 처리그룹에서 유의적으로 감소하였지만, 체중과 식이섭취량은 HFD+BCA 처리그룹에서 일정하게 유지되었다. 또한, 지방조직과 간조직에서 지방의 축적은 HFD+Vehicle처리그룹에 비하여 HFD+BCA 처리그룹에서 낮게 관찰되었다. 더불어, BCA 처리후에 유의적인 변화는 total cholesterol (TC)과 LDL에서 관찰되었지만, HDL의 농도는 BCA처리에 의해 변화가 없었다. 인슐린의 농도는 HFD+BCAMi 처리그룹과 비교하여 HFD+BCALo과 HFD+BCAMi 처리그룹에서 유의적으로 감소하였다. 따라서 이러한 결과는 한천식이섬유의 장기간 투여는 고지방사료를 급여한 동물에서 지방축적, 혈청내 지방프로파일, 인슐린농도의 개선을 유도할 수 있음을 제시하고 있다. 또한, 이러한 결과는 한천식이 섬유를 함유하는 음료는 혈청내 지질과 인슐린 작용을 유도할 수 있음을 제시하고 있다.

• Laboraroty Animal Research
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• 제34권4호
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• pp.288-294
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• 2018

A few clues about correlation between endoplasmic reticulum (ER) stress and mulberry (Morus alba) leaves were investigated in only the experimental autoimmune myocarditis and streptozotocin-induced diabetes. To investigate whether a novel extract of mulberry leaves fermented with Cordyceps militaris (EMfC) could suppress ER in fatty liver, alterations in the key parameters for ER stress response were measured in high fat diet (HFD)-induced obese C57L/6 mice treated with EMfC for 12 weeks. The area of adipocytes in the liver section were significantly decreased in the HFD+EMfC treated group as compared to the HFD+Vehicle treated group, while their level was higher in HFD+Vehicle treated group than No treated group. The level of the eukaryotic initiation factor 2 alpha ($eIF2{\alpha}$) and inositol-requiring enzyme 1 beta ($IRE1{\alpha}$) phosphorylation and CCAAT-enhancer-binding protein homologous protein (CHOP) expression were remarkably enhanced in the HFD+Vehicle treated group. However, their levels were restored in the HFD+EMfC treated group, although some differences were detected in the decrease rate. Similar recovery was observed on the ER stress-induced apoptosis. The level of Caspase-3, Bcl-2 and Bax were decreased in the HFD+EMfC and HFD+orlistat (OT) treated group compared to the HFD+Vehicle treated group. The results of the present study therefore provide first evidence that EMfC with the anti-obesity effects can be suppressed ER stress and ER stress-induced apoptosis in the hepatic steatosis of HFD-induced obesity model.

• 한국약용작물학회지
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• 제25권6호
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• pp.367-374
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• 2017

Background: An imbalance in energy intake and expenditure can cause obesity, which is a major risk factor for chronic diseases such as heart disease, type 2 diabetes, insulin resistance, cancers and hyperlipidemia. Methods and Results: In this study, we evaluated the anti-obesity effects of a water extract from the young leaves of barley sprout (BS) in 3T3-L1 cells and in high-fat diet (HFD)-induced obese mice (HF). Lipid accumulation measurement indicates that BS markedly inhibited adipogenesis by reducing lipid droplet production in a dose-dependent manner. Furthermore, the mRNA expression of adipogenic transcription factors peroxisome proliferator-activated receptor-${\gamma}$ and fatty acid synthetase, CCAAT/enhancer binding protein-${\alpha}$ and fatty acid binding protein 4 in 3T3-L1 cells was significantly inhibited by BS treatment. In an in vivo test, the BS-administered group of HFD-induced mice showed less body weight gain, and lower liver and epididymal white adipose tissue weights. The BS-treated mice showed decreased serum levels of leptin and lipids compared to untreated HFD mice and the levels of adiponectin and the HDL-cholesterol/total cholesterol ratio increased. These results indicate that BS inhibits body fat accumulation by reducing the mRNA expression of lipogenesis transcription factors and increasing serum adipokine concentration in in vitro and in vivo tests. Conclusions: BS reduced high fat diet-induced weight gain and had a positive effect on dyslipidemia.

• IMMUNE NETWORK
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• 제22권2호
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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.

• 한방재활의학과학회지
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• 제28권3호
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• pp.1-11
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• 2018

Objectives This study was designed to evaluate the efficacy of Seungyangjeseup-tang on obesity by using 3T3-L1 cells and high fat diet mice. Methods In vitro, Seungyangjeseup-tang extract (SYJST) (10, 50, 100, 200, 400, $800{\mu}g/mL$) ware added in 3T3-L1 cells. SYJST cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assasy. Adipocyte differentiation was measured by Oil Red-O staining. In vivo, the experimental animals were divided into five groups: normal diet-fed normal group (N), high-fat diet (HFD)-fed control group (Con), HFD+SYJST 100 mg/kg group (SY100), HFD+SYJST 200 mg/kg group (SY200), and HFD+olistat 60 mg/kg as a positive drug control group (Orli). Markers of obesity, such as body weight, liver weight, food intake, serum total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), liver tissue TC, TG and fecal TC, TG were measured. Results In vitro, cytotoxicity was not significant compared with the control group. 3T3-L1 cell's differentiation was significantly decreased in Oil Red-O staining. In vivo, compared with controls, mice treated with SYJST demonstrate lower body and liver weight, and reduced food intake. In addition, SYJST increased TC, TG in the serum but not significance. And SYJST showed decreasing tendency TC, TG in the liver tissue. Furthermore, SYJST increased TC, TG in the facal but not significance. Conclusions Based on the results above, Seungyangjeseup-tang may reduce adipocyte differentiation, body fat, food intake, liver weight in obesity. This suggests that Seungyangjeseup-tang may be clinically useful in obesity treatment.

• 한방재활의학과학회지
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• 제26권2호
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• pp.1-12
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• 2016

Objectives The purpose of this study was to evaluate anti-obesity effect of Galgeuntang (gegentang) and elucidate the effect of it on gene expression related to obesity. Methods The experiments were performed with the use of Diet-Induced Obese mice. They were grouped NC (normal control), HFD (high fat diet control), GGT (Galgeun-tang (gegentang), 700 mg/kg), ORL (Orlistat, 10 mg/kg). GGT was orally administered for 12 weeks. Body weight was measured every week. Real-time PCR was performed to investigate the effect of GGT on gene expression in liver tissue. Results GGT group and ORL group were reduced in body weight compared with HFD. HFD increased $PPAR{\gamma}$, SREBP-1, Leptin, aP2, FATP1, FAS gene expression compared with NC. GGT increased FATP1 gene expression. But GGT reduced $PPAR{\gamma}$ & FAS gene expression in liver tissue of diet-induced obese mice compared with HFD. Conclusions These results suggest that GGT is supposed to have a certain impact on the treatment of obesity. But more study is needed in the future.

• 문화기술의 융합
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• 제4권1호
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• pp.315-323
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• 2018

당뇨 환자의 급격한 증가는 한국의 주요 건강문제중 하나이다. 당뇨 예방 또는 치료용 식품개발에 대한 노력의 일환으로 본 연구에서는 고지방식이급여로 유도한 제2형 당뇨동물모델에서 커큐민의 항당뇨효능을 연구하였다. C57BL/6 마우스를 정상식이, 고지방식이, 그리고 고지방식이에 0.02% 커큐민을 급여한 군으로 나누고 각 식이를 총 16주간 급여하였다. 그 결과, 커큐민 급여군이 고지방식이급여군에 비해 체중 증가량, 혈당, 혈중 인슐린, 총콜레스테롤, LDL-콜레스테롤 농도가 유의적으로 감소하였고 반면에 HDL-콜레스테롤 수준은 증가하였다. 또한 커큐민의 급여는 인슐린 신호전달체계를 활성화시켰다. 이러한 결과는 커큐민이 인슐린 저항성을 일부 극복시킴으로써 비만과 연관된 제2형 당뇨병을 개선시킬 수 있음을 제시한다.

• Biomolecules & Therapeutics
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• 제27권2호
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• pp.134-144
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• 2019

The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with the incidence of obesity; however, the underlying mechanisms are unknown. In this study, high-resolution metabolomics (HRM) along with transcriptomics were applied on animal models to draw a mechanistic insight of NAFLD. Wild type (WT) and catalase knockout (CKO) mice were fed with normal fat diet (NFD) or high fat diet (HFD) to identify the changes in metabolic and transcriptomic profiles caused by catalase gene deletion in correspondence with HFD. Integrated omics analysis revealed that cholic acid and $3{\beta}$, $7{\alpha}$-dihydroxy-5-cholestenoate along with cyp7b1 gene involved in primary bile acid biosynthesis were strongly affected by HFD. The analysis also showed that CKO significantly changed all-trans-5,6-epoxy-retinoic acid or all-trans-4-hydroxy-retinoic acid and all-trans-4-oxo-retinoic acid along with cyp3a41b gene in retinol metabolism, and ${\alpha}/{\gamma}$-linolenic acid, eicosapentaenoic acid and thromboxane A2 along with ptgs1 and tbxas1 genes in linolenic acid metabolism. Our results suggest that dysregulated primary bile acid biosynthesis may contribute to liver steatohepatitis, while up-regulated retinol metabolism and linolenic acid metabolism may have contributed to oxidative stress and inflammatory phenomena in our NAFLD model created using CKO mice fed with HFD.

• Journal of Microbiology and Biotechnology
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• 제28권5호
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• pp.688-696
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• 2018

Ginseng and probiotics have anti-obesity effects in mice fed a high-fat diet (HFD). Absorption of ginsenoside and colonization of probiotics occur in the intestine. In this study, a mixture of fermented ginseng and two probiotics, Bifidobacterium longum BORI and Lactobacillus paracasei CH88, was administered to HFD-fed mice for 9 weeks. The mixture significantly suppressed weight gain (p < 0.05, n = 8) and lipid deposition in the liver and adipose tissues as well as increased the mice's food intake. The adipocyte size of the adipose tissue was significantly decreased in the mixture-fed group, especially when 0.5% fermented ginseng and $5{\times}10^8/ml$ of the two probiotics were used (p < 0.05, n = 10). The expression of TNF-${\alpha}$ in adipose tissue was efficiently downregulated in the mixture-fed group (p < 0.05, n = 4). The supplement also improved the mice's fasting blood glucose levels (p < 0.05, n = 8) and total cholesterol feces excretion (p < 0.05, n = 8). The mixture of fermented ginseng and B. longum BORI and L. paracasei CH88 could have an anti-obesity effect and suppress lipid deposit in the liver and adipose tissues.