• Journal of Ginseng Research
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• 제34권4호
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• pp.369-375
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• 2010

This study evaluated the protective effects of ginseng leaf extract (GLE) against high fat-diet-induced hyperglycemia and hyperlipidemia, and explored the potential mechanism underlying these effects in C57BL/6J mice. The mice were randomly divided into four groups: normal control, high fat diet control (HFD), GLE-treated at 250 mg/kg, and GLE-treated at 500 mg/kg. To induce hyperglycemic and hyperlipidemic states, mice were fed a high fat diet for 6 weeks and then administered GLE once daily for 8 weeks. At the end of the treatment, we examined the effects of GLE on plasma glucose, lipid levels, and the expression of genes related to lipogenesis, lipolysis, and gluconeogenesis. Both GLE groups lowered levels of plasma glucose, insulin, triglycerides, total cholesterol, and non-esterified fatty acids when compared to those in HFD group. Histological analysis revealed significantly fewer lipid droplets in the livers of GLE-treated mice compared with HFD mice. To elucidate the mechanism, Western blots and RT-PCR were performed using liver tissue. Compared with HFD mice, GLE-treated mice showed higher levels of phosphorylation of AMP-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase, but no differences in the expression of lipogenic genes such as sterol regulatory element-binding protein 1a, fatty acid synthase, sterol-CoA desaturase 1 and glycerol-3-phosphate acyltransferase. However, the expression levels of lipolysis and fatty acid uptake genes such as peroxisome proliferator-activated receptor-$\alpha$ and CD36 were increased. In addition, phosphoenolpyruvate carboxykinase gene expression was decreased. These results suggest that GLE ameliorates hyperglycemia and hyperlipidemia by inhibiting gluconeogenesis and stimulating lipolysis, respectively, via AMPK activation.

• Animal Bioscience
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• 제35권1호
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• pp.22-28
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• 2022

Objective: Endoplasmic reticulum (ER) stress engages the unfolded protein response (UPR) that serves as an important mechanism for modulating hepatic fatty acid oxidation and lipogenesis. Chronic fasting in mice induced the UPR activation to regulate lipid metabolism. However, there is no direct evidence of whether negative energy balance (NEB) induces ER stress in the liver of cows. This study aimed to elucidate the relationship between the NEB attributed to feed deprivation and ER stress in bovine hepatocytes. Methods: Blood samples and liver biopsy tissues were collected from 6 non-lactating cows before and after their starvation for 48 h. The blood non-esterified fatty acids (NEFA), β-hydroxybutyric acid (BHBA) and glucose level were analyzed. Real-time quantitative polymerase chain reaction and Western blotting were used to explore the regulation of genes associated with UPR and lipid metabolism. Results: The starvation increased the plasma BHBA and NEFA levels and decreased the glucose level. Additionally, the starvation caused significant increases in the mRNA expression level of spliced X-box binding protein 1 (XBP1s) and the protein level of phosphorylated inositol-requiring kinase 1 alpha (p-IRE1α; an upstream protein of XBP1) in the liver. The mRNA expression levels of peroxisome proliferator-activated receptor alpha and its target fatty acid oxidation- and ketogenesis-related genes were significantly upregulated by the starvation-mediated NEB. Furthermore, we found that the mRNA expression levels of lipogenic genes were not significantly changed after starvation. Conclusion: These findings suggest that in the initial stage of NEB in dairy cows, the liver coordinates an adaptive response by activating the IRE1 arm of the UPR to enhance ketogenesis, thereby avoiding a fatty liver status.

• BMB Reports
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• 제51권9호
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• pp.462-467
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• 2018

A previous study of ours indicated that Drosophila flightless-1 controls lipid metabolism, and that there is an accumulation of triglycerides in flightless-1 (fliI)-mutant flies, where this mutation triggers metabolic stress and an obesity phenotype. Here, with the aim of characterizing the function of FliI in metabolism, we analyzed the levels of gene expression and metabolites in fliI-mutant flies. The levels of enzymes related to glycolysis, lipogenesis, and the pentose phosphate pathway increased in fliI mutants; this result is consistent with the levels of metabolites corresponding to a metabolic pathway. Moreover, high-throughput RNA sequencing revealed that Drosophila FliI regulates the expression of genes related to biological processes such as chromosome organization, carbohydrate metabolism, and immune reactions. These results showed that Drosophila FliI regulates the expression of metabolic genes, and that dysregulation of the transcription controlled by FliI gives rise to metabolic stress and problems in the development and physiology of Drosophila.

• Biomolecules & Therapeutics
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• 제24권6호
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• pp.650-658
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• 2016

Chronic alcohol consumption causes alcoholic liver disease, which is associated with the initiation of dysregulated lipid metabolism. Recent evidences suggest that dysregulated cholesterol metabolism plays an important role in the pathogenesis of alcoholic fatty liver disease. Ecklonia stolonifera (ES), a perennial brown marine alga that belongs to the family Laminariaceae, is rich in phlorotannins. Many studies have indicated that ES has extensive pharmacological effects, such as antioxidative, hepatoprotective, and antiinflammatory effects. However, only a few studies have investigated the protective effect of ES in alcoholic fatty liver. Male Sprague-Dawley rats were randomly divided into normal diet (ND) (fed a normal diet for 10 weeks) and ethanol diet (ED) groups. Rats in the ED group were fed a Lieber-DeCarli liquid diet (containing 5% ethanol) for 10 weeks and administered ES extract (50, 100, or 200 mg/kg/day), silymarin (100 mg/kg/day), or no treatment for 4 weeks. Each treatment group comprised of eight rats. The supplementation with ES resulted in decreased serum levels of triglycerides (TGs), total cholesterol, alanine aminotransferase, and aspartate aminotransferase. In addition, there were decreases in hepatic lipid and malondialdehyde levels. Changes in liver histology, as analyzed by Oil Red O staining, showed that the ES treatment suppressed adipogenesis. In addition, the ES treatment increased the expression of fatty acid oxidation-related genes (e.g., PPAR-${\alpha}$ and CPT-1) but decreased the expression of SREBP 1, which is a TG synthesis-related gene. These results suggest that ES extract may be useful in preventing fatty acid oxidation and reducing lipogenesis in ethanol-induced fatty liver.

• Nutrition Research and Practice
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• 제16권3호
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• pp.314-329
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• 2022

BACKGROUND/OBJECTIVES: Oocyte lipid droplets play a crucial role in meiosis and embryo development. Biotin is associated with fatty acid synthesis and is the coenzyme for acetyl-CoA carboxylase (ACC). The effects of a biotin deficiency on the oocyte lipid metabolism remain unknown. This study examined the effects of a biotin deficiency and its replenishment on murine 1) oocyte lipid droplet levels, 2) ovary lipid metabolism, and 3) oocyte meiosis. MATERIALS/METHODS: Mice were divided into 3 groups: control, biotin deficient (BD), and recovery groups. The control and BD groups were fed a control diet or BD diet (0.004 or 0 g biotin/kg), respectively. The recovery group mice were fed a BD diet until day 21, and were then fed the control diet from days 22 to 64. This study then quantified the oocyte lipid droplet levels, assessed the oocyte mitochondrial function, and examined the ability of oocytes to undergo meiosis. Ovarian phosphorylated ACC (p-ACC), lipogenesis, β-oxidation, and ATP production-related genes were evaluated. RESULTS: The BD group showed a decrease in lipid droplets and mitochondrial membrane potential and increased p-ACC levels. In the recovery group, the hepatic biotin concentration, ovarian p-ACC levels, and mitochondrial membrane potential were restored to the control group levels. On the other hand, the quantity of lipid droplets in the recovery group was not restored to the control levels. Furthermore, the percentage of oocytes with meiotic abnormalities was higher in the recovery group than in the control group. CONCLUSIONS: A biotin deficiency reduced the oocyte lipid droplet levels by downregulating lipogenesis. The decreased lipid droplets and increased oocyte meiosis failure were not fully restored, even though the biotin nutrition status and gene expression of lipid metabolism was resumed. These results suggest that a biotin deficiency remains robust and can be long-lasting. Biotin might play a crucial role in maintaining the oocyte quality.

• 생명과학회지
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• 제34권1호
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• pp.1-8
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• 2024

Brain-type natriuretic peptide (BNP)은 뇌나트륨이뇨펩티드로, 좌심실의 심근세포에서 분비되는 호르몬으로, 심장과 신장에 작용하여 혈관 확장과 나트륨 이뇨 작용 등을 하는 것으로 알려져 있으나, 최근에는 다양한 조직에서 대사 작용을 조절하는 것으로 보고된다. 본 연구에서는 간 조직에서 BNP의 영향을 알기 위해 BNP가 고지방식이에 의해 유도되는 인슐린 저항성을 개선하는지를 조사하였다. BNP을 주입한 쥐와 control로서 saline을 주입한 쥐들 간에는 몸무게, 체지방양(fat mass), 제지방량(lean body mass)의 변화는 없었다. 고인슐린혈증 정상혈당 글루코스 클램프(Hyperinsulinemic Euglycemic Glucose Clam) 동안, BNP를 주입한 고지방 식이 쥐들은 saline을 주입한 고지방식이 쥐에 비해 혈당(blood glucose)은 감소하였으며, 포도당 주입 속도(glucose infusion rate)는 증가하였다. 또한 BNP은 포도당 신생 및 중성지방 합성 관련 유전자들의 발현을 감소시켜, 간에서 포도당 생성과 중성지방의 양을 감소시켰다. BNP는 saline을 주입한 쥐에 비해 간 조직에서 Akt와 AMP-activated protein kinase (AMPK)의 인산화를 증가시켰는데, 이는 BNP을 처리한 AML12 간세포에서도 BNP는Akt와 AMPK 인산화를 증가시켰다. 이상의 결과는 BNP가 간에서 인슐린 저항성을 개선하여 포도당 생성과 중성 지방 생성을 억제함을 알 수 있었다.

• 동의생리병리학회지
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• 제22권3호
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• pp.642-648
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• 2008

The aim of this study is to investigate Chegameuiin-tang water extracts (CETE) have potent anti-obesity activities in a high fat diet-induced obesity mouse model. In this study, we designed three group (normal diet group, high fat diet group, high fat diet plus CETE group for 13-week oral administration). Increases in body weight and fat storage were inhibited by 13-week oral administration of CETE at a 500 mg/kg concentration in this animal model, while the amount of food intake was not affected. Results from blood lipid analysis showed that the levels of triglyceride, total cholesterol and LDL-cholesterol were significantly lowered by CETE administration, also HDL-cholesterol was increased more than high fat diet-induced obese mouse. To understand the underlying mechanism at the molecular level, the effects of CETE were examined on the expression of the genes involved in lipogenesis and lipolysis by real-time PCR. In epididymal fat of CETE-treated mice, the mRNA level of lipogenic genes such as sterol regulatory element binding protein 1 and fatty acid synthase were decreased, which was well correlated with the reduction of the epididymal fat weight. Also, CETE administration inhibited decreases of the hormone-sensitve lipase and lipoprotein lipase mRNA expressions, which are genes related with lipolysis. These results suggest that Chegameuiin-tang may have great potential as a novel anti-obesity agent.

• 한국미생물·생명공학회지
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• 제50권1호
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• pp.135-146
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• 2022

비만은 지질대사 불균형으로 인한 이상지질혈증과 밀접한 관련이 있으며, 장내 미생물의 군집 및 기능의 변화를 유도하여 장내 미생물 불균형을 초래할 수 있다. 본 연구에서는 민들레 김치에서 분리한 김치 유래 유산균 W. confuse WIKIM51의 항비만 효능을 in vitro와 in vivo에서 평가하였다. 먼저, WIKIM51은 지방세포 분화를 유도한 3T3-L1 세포에서 지방대사 관련 유전자의 발현 조절을 통해 지방구 생성을 억제하였다. 후천적 비만 동물 모델을 이용한 in vivo 실험에서 10주간 W. confusa WIKIM51의 경구 투여는 고지방식이에 의해 유도된 체중 증가를 현저히 감소시켰다. 특히, 부고환 주위 지방량, 조직학적 분석을 통한 지방구의 크기 및 혈중 지표인 TG, TC, adiponectin, 그리고 leptin의 수준이 HFD군에 비해 W. confusa WIKIM51 섭취군에서 유의적으로 개선되었다. 또한 W. confusa WIKIM51 섭취군은 Ppar𝛾, C/EBP𝛼, Srebp-1c, Fas와 같은 지방 생성 및 지방산 합성 관련 유전자의 발현을 억제하였고, 반면 에너지 소비 관련 유전자 Ppar𝛼와 Cpt1의 발현은 증가시켰다. 더 나아가, W. confusa WIKIM51은 고지방식이로 인해 유도된 Firmicutes/Bacteroidetes 비율을 정상식이군의 수준으로 감소시켜 장내미생물의 불균형을 개선시켰다. 이러한 결과들을 종합해 볼 때, W. confusa WIKIM51의 섭취는 고지방식이로 인한 지방 축적을 억제하여 효과적으로 비만을 개선할 수 있으며, 이는 항비만 기능성 소재 및 식품 개발로의 활용이 가능함을 제시한다.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.369-378
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• 2023

본 연구는 청가시덩굴 에탄올 추출물을 이용하여 3T3-L1 지방전구세포에서 지방세포를 통해 항비만 활성을 확인하고자 하였다. 청가시덩굴 에탄올 추출물에 의한 지방세포 분화 억제 활성 및 지방형성에 미치는 영향을 확인하기 위해 3T3-L1 지방전구세포에 분화를 유도하여 추출물을 농도별로 처리하였다. 그 결과 청가시덩굴 에탄올 추출물 처리 시 지방세포 분화 및 세포 내 중성지방 축적 수준이 농도 의존적으로 감소하였다. 이러한 지방형성 억제 효과가 어떠한 작용기전에 의해 유도되는지 확인하기 위해 청가시덩굴 추출물과 그로부터 분리된 화합물인 acertannin을 이용하여 지방세포 분화 조절인자들의 유전자 및 단백질 발현을 확인하고자 하였다. 청가시덩굴 에탄올 추출물은 지방형성 및 지방산 합성 관련 인자인 PPARγ, C/EBPα, ADD1/SREBP1c, FAS, aP2의 유전자 및 단백질 발현을 유의적으로 억제하였다. 이러한 결과들로 볼 때 청가시덩굴 에탄올 추출물은 지방세포분화 및 지방축적 인자의 조절 효과를 나타냄으로써 산림자원의 항비만 및 고지혈증 개선 기능성 소재로의 활용 가능성을 확인하였다.

• Asian-Australasian Journal of Animal Sciences
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• 제22권10호
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• pp.1420-1428
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• 2009

In this study we cloned and characterized a novel lipid-accumulating gene, the oxidized low-density lipoprotein receptor 1 (OLR1), which is associated with lipogenesis. We analyzed the gene structure and detected the mRNA transcriptional expression levels in pig adipose tissues at different months of age (MA) and in different economic types (lean type and obese type) using real-time fluorescence quantitative PCR. OLR1 expression profile in different tissues of pig was analyzed. Finally, we studied the correlation between OLR1 and lipid metabolism related genes including peroxisome proliferator-activated $receptor{\gamma}2$ ($PPAR{\gamma}2$), fatty acid synthetase (FAS), triacylglycerol hydrolase (TGH), CAAT/enhancer binding protein $\alpha$ ($C/EBP{\alpha}$) and sterol regulatory element binding protein-1c (SREBP-1c). Results indicated that the OLR1 gene of the pig exhibited the highest homology with the cattle (84%), and the lowest with the mouse (27%). The signal peptide located from amino acid 38 to 60 and the domain from amino acid 144 to 256 were shared by the C-type lectin family. The expression level of OLR1 in pig lung was exceedingly higher than other tested tissues (p<0.01). In pig adipose tissue, the expression level of OLR1 mRNA increased significantly with growth (p<0.01). The expression level of OLR1 mRNA in obese-type pigs was significantly higher than that of lean-type pigs of the same monthly age (p<0.05). In adipose tissue, the expression of OLR1 correlated with $PPAR{\gamma}2$, FAS and SREBP-1c, but not TGH or C/EBP${\alpha}$. In conclusion, OLR1 was highly associated with fat deposition and its transcription, as suggested by high correlations, was possibly regulated by $PPAR{\gamma}2$ and SREBP-1c.