• Journal of Ginseng Research
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• 제32권3호
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• pp.187-193
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• 2008

The present study was designed to investigate the anti-diabetic effect and mechanism of Korean red ginseng in C57BL/KsJ db/db mice. The db/db mice were divided into three groups: diabetic control group (DC), Korean red ginseng group (KRG, 100 mg/kg) and metformin group (MET, 300 mg/kg), and treated with drugs once per day for 10 weeks. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in KRG-, 67.7% in MET-treated group. With decreased plasma glucose and insulin levels, the insulin resistance index of the KRG-treated group was reduced by 27.6% compared to the DC group. The HbA1c levels in KRG and MET-treated groups were also decreased by 11.0% and 18.9% compared to that of DC group, respectively. Plasma triglyceride and non-esterified fatty acid levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the KRG-treated group compared to those in DC group. Histological analyses of the liver and fat tissue of mice treated with KRG revealed significantly decreased number of lipid droplets and decreased size of adipocytes compared to the DC group. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin contents, but decreased glucagon production. To elucidate action mechanism of KRG, effects on AMP-activated protein kinase (AMPK) and its downstream target proteins responsible for fatty acid oxidation and gluconeogenesis were explored in the liver. KRG activated AMPK and acetyl-coA carboxylase (ACC) phosphorylations, resulting in stimulation of fatty acid oxidation. KRG also caused to down regulation of SREBP1a and its target gene expressions such as FAS, SCD1 and GPAT. In summary, our results suggest that KRG exerted the anti-diabetic effect through AMPK activation in the liver of db/db mice.

• Journal of Nutrition and Health
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• 제51권4호
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• pp.275-286
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• 2018

본 연구는 떫은감 청도반시의 분말을 열수 추출하고 칼럼 추출하는 과정에서 획득한 PWE와 TEP에 대한 대사체 프로파일을 분석하고, 유리지방산을 처리한 HepG2 세포와 식이로 고지혈증을 유도한 Wistar계 흰쥐의 간조직을 사용하여 중성지질 및 콜레스테롤 대사 관련 유전자 발현을 측정하였다. 대사체 분석은 가스크로마토그래프-질량분석법과 액체크로마토그래프-질량분석법을 사용하였으며, PLS-DA 분석과 heatmap 분석을 실시한 결과 PWE는 떫은감 분말과 비교적 유사한 대사체 프로파일을, 그리고 TEP는 떫은감 분말과 매우 다른 대사체 프로파일을 가지고 있음을 확인하였다. 세포실험과 또한 세포실험에서 얻어진 결과를 검증하기 위해 수행된 동물실험에서 PWE와 TEP는 모두 SREBP1c와 FAS 유전자 발현을 감소하여 간의 지방축적을 감소시키는 것으로 관찰되었으나, 콜레스테롤 축적을 억제하는 효능은 PWE에 비해 TEP에서 우세하게 증가하는 것이 관찰되었다. 특별히 TEP는 SREBP2, HMGCR 유전자 발현을 억제하고 LDLR 유전자 발현을 촉진하는 것으로 나타났다. TEP는 탄닌 중 Gallic acid 그리고 장쇄지방산아미드인 Oleamide와 Palmitamide 함량이 유의하게 증가되었으므로, 향후 이들 성분과 타깃 유전자의 상관성을 분석하고, 이를 통해 시스템네트워크로 나타내어 대사체 프로파일에 따른 지질 및 콜레스테롤 대사 간 상호 영향을 추가적으로 연구해야 할 것으로 사료된다.

• Nutrition Research and Practice
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• 제13권3호
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• pp.196-204
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• 2019

BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disease triggered by epigenetic alterations, including lysine acetylation at histone or non-histone proteins, affecting the stability or transcription of lipogenic genes. Although various natural dietary compounds have anti-lipogenic effects, their effects on the acetylation status and lipid metabolism in the liver have not been thoroughly investigated. MATERIALS/METHODS: Following oleic-palmitic acid (OPA)-induced lipid accumulation in HepG2 cells, the acetylation status of histone and non-histone proteins, HAT activity, and mRNA expression of representative lipogenic genes, including $PPAR{\gamma}$, SREBP-1c, ACLY, and FASN, were evaluated. Furthermore, correlations between lipid accumulation and HAT activity for 22 representative natural food extracts (NExs) were evaluated. RESULTS: Non-histone protein acetylation increased following OPA treatment and the acetylation of histones H3K9, H4K8, and H4K16 was accelerated, accompanied by an increase in HAT activity. OPA-induced increases in the mRNA expression of lipogenic genes were down-regulated by C-646, a p300/CBP-specific inhibitor. Finally, we detected a positive correlation between HAT activity and lipid accumulation (Pearson's correlation coefficient = 0.604) using 22 NExs. CONCLUSIONS: Our results suggest that NExs have novel applications as nutraceutical agents with HAT inhibitor activity for the prevention and treatment of NAFLD.

• Journal of the Korean Data and Information Science Society
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• 제26권3호
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• pp.677-685
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• 2015

인간의 질병 또는 가축의 경제적인 특성은 단일 유전자보다는 여러 유전자들의 상호작용에 의한 영향을 많이 받는다. 본 연구에서는 이러한 유전자들의 상호작용을 규명하기 위해 기존에 사용되었던 방법들의 단점을 보완한 에스엔피 하비스트 방법을 이용하였다. 사용된 유전자는 최근 한우의 육질에 영향을 미치는 지방산 조성과 깊은 연관이 있다고 밝혀진 단일염기다형성 중 SREBPs (g.3270+10274 C>T, g.13544 T>C)와 FABP4 (g.2634+1018 A>T, g.2988 A>G, g.3690 G>A, g.3710 G>C, g.3977-325 T>C, g.4221 A>G)이며, 경제형질은 한우의 맛과 향에 영향을 주는 올레인산, 불포화지방산, 근내지방도를 이용하였다. 먼저 에스엔피 하비스트 방법을 이용하여 경제형질에 영향을 주는 우수 유전자 조합을 찾은 뒤 다중인자차원축소방법을 이용하여 단일염기다형성 조합 내의 우수 유전자형도 함께 규명하였다.

• 동의생리병리학회지
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• 제28권3호
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• pp.288-295
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• 2014

Bojungchiseub-tang (BJCST) has been used in symptoms and signs of edema, dampness-phlegm, kidney failure, and so on. BJCST is also expected to have strong anti-obesity activities. However, little is known about the mechanisms of its inhibitory effects on adipocyte differentiation and adipogenesis. In the present study, we examined the effects and mechanism of BJCST on transcription factors and adipogenic genes of 3T3-L1 preadipocytes to understand its inhibitory effects on adipocyte differentiation and adipogenesis. Our results showed that BJCST significantly inhibited differentiation and adipogenesis of 3T3-L1 preadipocytes in a dose-dependent manner. To elucidate the mechanism of the effects of BJCST on lowering lipid content in 3T3-L1 adipocytes, we examined whether BJCST modulate the expressions of transcription factors to induce adipogenesis and adipogenic genes related to regulate accumulation of lipids. As a result, the expression of steroid regulatory element-binding protein (SREBP)1, cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT)/enhancer binding proteins ${\alpha}$ ($C/EBP{\alpha}$), $C/EBP{\beta}$, $C/EBP{\delta}$, and peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) genes, which induce the adipose differentiation, liver X receptor $(LXR){\alpha}$ and fatty acid synthase (FAS) genes, which induce lipogenesis and adipose-specific aP2, Adipsin, lipoprotein lipase (LPL), CD36, TGF-${\beta}$, leptin and adiponectin genes, which compose fat formation were decreased. BJCST also reduced the expression of acyl CoA oxidase (ACO) and uncoupling protein (UCP) genes related to lipid oxidation. In conclusion, BJCST could regulate transcript factor related to induction of adipose differentiation and inhibited the accumulation of lipids and expression of adipogenic genes.

• Nutrition Research and Practice
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• 제15권5호
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• pp.568-578
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• 2021

BACKGROUND/OBJECTIVES: Psidium guajava L. (guava) leaves have been shown to exhibit hypoglycemic and antidiabetic effects in rodents. This study investigated the effects of guava leaf extract on adipogenesis, glucose uptake, and lipolysis of adipocytes to examine whether the antidiabetic properties are mediated through direct effects on adipocytes. MATERIALS/METHODS: 3T3-L1 cells were treated with 25, 50, 100 ㎍/mL of methanol extract from guava leaf extract (GLE) or 0.1% dimethyl sulfoxide as a control. Lipid accumulation was evaluated with Oil Red O Staining and AdipoRed assay. Immunoblotting was performed to measure the expression of adipogenic transcription factors, fatty acid synthase (FAS), and AMP-activated protein kinase (AMPK). Glucose uptake under basal or insulin-stimulated condition was measured using a glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose. Lipolysis from fully differentiated adipocytes was measured by free fatty acids release into the culture medium in the presence or absence of epinephrine. RESULTS: Oil Red O staining and AdipoRed assay have shown that GLE treatment reduced lipid accumulation during adipocyte differentiation. Mitotic clonal expansion, an early essential event for adipocyte differentiation, was inhibited by GLE treatment. GLE inhibited the expression of transcription factors involved in adipocyte differentiation, such as peroxisome proliferator-activated receptor 𝛄 (PPAR𝛄), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein-1c (SREBP-1c). FAS expression was also decreased while the phosphorylation of AMPK was increased by GLE treatment. In addition, GLE increased insulin-induced glucose uptake into adipocytes. In lipid-filled mature adipocytes, GLE enhanced epinephrine-induced lipolysis but reduced basal lipolysis dose-dependently. CONCLUSIONS: The results show that GLE inhibits adipogenesis and improves adipocyte function by reducing basal lipolysis and increasing insulin-stimulated glucose uptake in adipocytes, which can be partly associated with antidiabetic effects of guava leaves.

• KSBB Journal
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• 제24권6호
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• pp.549-555
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• 2009

본 연구에서는 신생혈관형성 제어에 바탕을 둔 비만세포제어 정도를 확인하기 위하여 4가지 지역 천연산물인 전호(Anthrisci radix), 파고지 (Psoraleae semen), 희첨 (Siegesbeckiae herba) 및 산수유 (Corni fructus)를 이용한 지방 축적물 변화 및 기전을 확인하기 위해 3T3-L1 adipocyte를 이용한 Oil Red O 염색 및 western blot을 실시하였다. 그 결과 전호, 파고지, 희첨, 산수유의 세포 독성 이내의 농도 증가에 따라 지방 축적물이 감소됨을 보였다. 또한 western blot을 위해 lipogenesis와 관련된 SREBP-1 및 adipogenesis와 관련된 $PPAR\gamma$와 C/$EBP\alpha$의 신호전달 정도를 확인한 결과 4가지 지역 천연산물의 농도 증가에 따라 단백질의 발현양이 감소됨을 확인하였다. 이는 4가지 지역 천연산물 추출물이 지방분화와 관련된 신호분자를 차단함으로써 지방형성이 억제되었음을 보였다. 따라서 4가지 지역 천연산물인 전호, 파고지, 희첨 및 산수유는 신생혈관형성 억제에 따른 항비만제제로서의 이용 가능함을 시사하였다.

• 동의생리병리학회지
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• 제30권4호
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• pp.279-288
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• 2016

To observe the potential hepatoprotective effects of Gongjin-dan on the acute ethanol (EtOH)-induced liver damages in C57BL/6 mice with its possible action mechanisms. EtOH-mediated acute hepatic damages were induced by oral administration of EtOH total 3 doses. The changes on the body weight, liver weight, albumin, TG, AST, ALP, ALT, hepatic TG contents, hepatic antioxidant defense system, TNF-α, CYP 2E1 activity and mRNA expressions of hepatic lipogenic genes - SREBP-1c, SCD1, ACC1, FAS, PPARγ and DGAT2 or genes involved in fatty acid oxidation - PPARα, ACO and CPT1 were observed with final liver histopathological inspections after 15 days of continuous administration of silymarin 200 mg/kg, Gongjin-dan (GJD) 400, 200 and 100 mg/kg. The results were compared with silymarin 200 mg/kg treated mice. Marked decreases of body and liver weights, increases of serum AST, ALT, Albumin and TG levels, hepatic TG contents, TNF-α level, CYP 2E1 activity and mRNA expressions of hepatic lipogenic genes or decreases mRNA expressions of genes involved in fatty acid oxidation were observed with histopathological changes related hepatosteatosis increases of immunolabelled hepatocytes, as the results of a binge drinking of EtOH in the present study. Also destroys of hepatic antioxidant defense systems were demonstrated in EtOH control mice as compared with intact vehicle control mice, respectively. The results suggest that oral administration of 400, 200 and 100 mg/kg of GJD favorably protected the liver damages from acute mouse EtOH intoxications.

• 대한한방소아과학회지
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• 제24권3호
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• pp.92-105
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• 2010

Objectives: The purpose of this study is to investigate the effects of Daecheongryong-tang (DCRT) on the adipogenesis in 3T3-L1 preadipocytes. Methods: 3T3-L1 preadipocytes were differentiated with adipogenic reagents by incubating for 2 days in the absence or presence of DCRT ranging 0.25 and 2%. The effect of DCRT on adipogenesis was examined by Oil red O staining, and the protein, RNA, and RT-PCR were measured. Results: Our results showed that DCRT decreased the TG content by ORO staining. To elucidate the mechanism of the effects of DCRT on lowering TG content in 3T3-L1 adipocytes, we examined the DCRT modulate expressions of transcription factors to induce adipogenesis and adipogenic genes which is related to the regulation of accumulation of lipids. As a result, the expression of SREBP1, C/$EBP{\beta}$, C/$EBP{\delta}$, C/$EBP{\alpha}$, and $PPAR{\gamma}$ genes, which induce the adipose differentiation and adipose-specific aP2, adipsin, LPL, CD36, TGF-${\beta}$ and adiponectin genes which regulates fat formations, were decreased. In addition, DCRT reduced the expression of iNOS and IL-6 in 3T3-L1 adipocytes, resulting in inflammation. Conclusions: DCRT could regulate transcript factor related to induction of adipose differentiation, inhibit the accumulation of lipids and expression of the adipogenic genes.

• 한국약용작물학회지
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• 제24권4호
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• pp.309-316
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• 2016

Background: This study represents the first report that the anti-obesity activity of ethanol extracts of Aronia melanocarpa can be enhanced through ultrasonification at a frequency of 120 kHz at $60^{\circ}C$ (UE). Methods and Results: The amounts of cyanidin-3-O-galactose (cya-gal), a major anthocyanin in A. melanocarpa were higher by up to 402.4 mg/100 g, as compared with 221.4 mg/100 g and 322.1 mg/100 g, for hot water at $100^{\circ}C$ and 70% ethanol at $80^{\circ}C$ respectively. This result should cause the higher antioxidant activities of the UE than extract of hot water and ethanol in DPPH free radical scavenging. It was confirmed that the high antioxidant activity of UE could play an important role in inhibiting the production of proteins related to adipocyte differentiation, such as peroxisome proliferator activated receptor-${\gamma}$ (PPAR-${\gamma}$) and sterol regulatory element binding protein 1 (SREBP1). Conclusions: Ultrasonification at a frequency of 120 kHz at $60^{\circ}C$ should result in better anti-obesity activity than that observed using other processes. It was also observed for the first time that the anti-obesity activity of A. melanocarpa was associated with its antioxidant activity, possibly due to the higher elution of intact cya-gal, owing to efficient low temperature ultrasonification extraction. These results could also be applied to improve other biological activities of medicinal herbs that contain many types of heat-labile bioactive substances.