• Biomolecules & Therapeutics
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• v.27 no.4
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• pp.386-394
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• 2019

Trypanosoma cruzi infection results in debilitating cardiomyopathy, which is a major cause of mortality and morbidity in the endemic regions of Chagas disease (CD). The pathogenesis of Chagasic cardiomyopathy (CCM) has been intensely studied as a chronic inflammatory disease until recent observations reporting the role of cardio-metabolic dysfunctions. In particular, we demonstrated accumulation of lipid droplets and impaired cardiac lipid metabolism in the hearts of cardiomyopathic mice and patients, and their association with impaired mitochondrial functions and endoplasmic reticulum (ER) stress in CD mice. In the present study, we examined whether treating infected mice with an ER stress inhibitor can modify the pathogenesis of cardiomyopathy during chronic stages of infection. T. cruzi infected mice were treated with an ER stress inhibitor 2-Aminopurine (2AP) during the indeterminate stage and evaluated for cardiac pathophysiology during the subsequent chronic stage. Our study demonstrates that inhibition of ER stress improves cardiac pathology caused by T. cruzi infection by reducing ER stress and downstream signaling of phosphorylated eukaryotic initiation factor ($P-elF2{\alpha}$) in the hearts of chronically infected mice. Importantly, cardiac ultrasound imaging showed amelioration of ventricular enlargement, suggesting that inhibition of ER stress may be a valuable strategy to combat the progression of cardiomyopathy in Chagas patients.

• The Korea Journal of Herbology
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• v.31 no.4
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• pp.11-18
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• 2016

Objectives : The objective of this study was to investigate the effect of Myrrh 80% ethanol extract on adipocyte differentiation and adipogenesis in 3T3-L1 cell.Methods : Myrrh was prepared by extracting with 80% ethanol. Cell viability was assessed by MTT assay using 3T3-L1 cells. Anti-obesity activity was measured in lipid droplets and triglyceride (TG) accumulation in 3T3-L1 cells. We also analyzed the expression of C/EBPβ, C/EBPα, PPARγ, SREBP1c, and aP2 by reverse transcriptase polymerase chain reaction (RT-PCR). In addition, we observed the production of fatty acid, acetyl-CoA carboxylase and Oil-red O stainingResults : No cytotoxicity from Myrrh 80% ethanol extracts was observed at the concentration of 1, 10, 100 (㎍/㎖) in 3T3-L1 cells. Treatment with Myrrh significantly suppressed the terminal differentiation of 3T3-L1 in a dose-dependent manner, as confirmed by a decrease in triglyceride and Fatty acid and Acetyl-CoA carboxylase. Also, Myrrh exhibited potential adipogenesis inhibition and downregulated the expression of pro-adipogenic transcription factors, such as sterol regulatory element binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer binding proteins α (C/EBPα) and C/EBPβ, and adipocyte expressed genes, such as adipocyte fatty acid binding protein (aP2) and Fas. In addition, lipid accumulation determined by Oil-red O staining showed that Myrrh extract had inhibitory effects on lipid accumulation in 3T3-L1 cells.Conclusions : These results suggest that Myrrh suppresses obesity factors in 3T3-L1 cells. Myrrh may be a useful medical herbs for attenuating metabolic diseases such as obesity.

• Korean Journal of Food Science and Technology
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• v.30 no.3
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• pp.693-696
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• 1998

Chitosan is the deacetylated product of chitin. Chitosan and its derivatives have many properties that make them attractive for a wide variety of health applications. This study was performed to investigate some effects of water soluble chitooligosaccharides on liver function in the mouse. The animals given the sterol diet containing 3% cholesterol for 6 weeks showed increase in plasma cholesterol level, which were lowered by 23% when they were fed on 1% chotooligosaccharide. While there was no significant change in liver cholesterol and plasma HDL-cholesterol levels. Continuous administration of 15% ethanol via drinking water to mice for 8 weeks elicited pathological alterations such as inflammation, necrosis, accumulation of lipid droplets in the liver and increase in GPT activity, while simultaneous administration of ethanol and chitooligosaccharide prevented remarkedly ethanol-induced liver injury; there was no observable lipid droplet and GPT activity was decreased by 25% in the liver. These results suggest that chitooligosaccharide play some roles in liver function, such as reducing the plasma cholesterol level and preventing alcoholic liver disease.

• Molecules and Cells
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• v.43 no.3
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• pp.286-297
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• 2020

Mammalian patatin-like phospholipase domain containing proteins (PNPLAs) play critical roles in triglyceride hydrolysis, phospholipids metabolism, and lipid droplet (LD) homeostasis. PNPLA7 is a lysophosphatidylcholine hydrolase anchored on the endoplasmic reticulum which associates with LDs through its catalytic region (PNPLA7-C) in response to increased cyclic nucleotide levels. However, the interaction of PNPLA7 with LDs through its catalytic region is unknown. Herein, we demonstrate that PNPLA7-C localizes to the mature LDs ex vivo and also colocalizes with pre-existing LDs. Localization of PNPLA7-C with LDs induces LDs clustering via non-enzymatic intermolecular associations, while PNPLA7 alone does not induce LD clustering. Residues 742-1016 contains four putative transmembrane domains which act as a LD targeting motif and are required for the localization of PNPLA7-C to LDs. Furthermore, the N-terminal flanking region of the LD targeting motif, residues 681-741, contributes to the LD targeting, whereas the C-terminal flanking region (1169-1326) has an anti-LD targeting effect. Interestingly, the LD targeting motif does not exhibit lysophosphatidylcholine hydrolase activity even though it associates with LDs phospholipid membranes. These findings characterize the specific functional domains of PNPLA7 mediating subcellular positioning and interactions with LDs, as wells as providing critical insights into the structure of this evolutionarily conserved phospholipid-metabolizing enzyme family.

• Korean Journal of Veterinary Research
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• v.35 no.3
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• pp.489-496
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• 1995

Artemisia messes-schmidiana var viridis(Compositae) has been used for jaundice, hepatitis, diuretic and liver cirrhosis etc. 1-naphthylisothiocyanate(ANIT) has been used as a model compound to study mechanisms of intrahepatic cholestasis in laboratory animals as rat and mouse. The purposes of present study are to examine pharmacological effects of Artemisia messes-schmidiana var viridis water extract(AMWE) on alterations of triacylglycerol, cholesterol, protein, albumin and A/G ratio levels in serum, of histopathological appearances of liver, and that of hepatic microsomal cytochrome P-450 contents. Increased serum triacylglycerol levels by ANIT were significantly decreased with AMWE. However, AMWE posttreatment aggravated ANIT-induced cholesterol increase. Serum total protein and albumin contents, and A/G ratio were decreased in all ANIT-treated groups, and there were increased compared with control by AMWE posttreatment. Hepatic microsomal cytochrome P-450 contents were decreased in either AMWE and ANIT treatment, which greatly increased with AMWE pretreatment. On the other hand, in histological findings, our results shown that ANIT induced increase of lipid droplets and widening of sinusoidal capillary and these phenomena were disappeared with AMWE treatment. In conclusion, AMWE have choleresis effect. Also, AMWE improved lipid metabolism, protection and regeneration of hepatocytes in ANIT-induced cholestasis.

• Toxicological Research
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• v.27 no.4
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• pp.211-216
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• 2011

Herbal medicines are widely used in many countries for the treatment of many diseases. Although the use of herb extracts as alternative medicine is growing, their toxicological properties have not been thoroughly investigated. In this study, we have investigated the effects of water and ethanol extracts of 18 herbs on the hepatic lipid metabolism and steatogenic hepatotoxicity. Ethanol extracts of Cirsium japonicum, Carthamus tinctorius, Rehmanniae glutinosa (preparata), Polygala tenuifolia, Foeniculum vulgare, Polygonum multiflorum, and Acorus gramineus and water extracts of Polygonum multiflorum and Rehmanniae glutinosa induced lipid accumulation in Sk-hep1 human hepatoma cells as determined by Nile red staining. These extracts increased the luciferase activity of sterol regulatory element (SRE) and decreased that of peroxisome proliferator response element (PPRE), indicating the possibilities of enhanced fatty acid synthesis and decreased fatty acid oxidation. To identify the components responsible for the fat accumulation, we tested 50 chemicals isolated from the nine herbs. Apigenin, luteolin, pectolinarin and lupeol from Cirsium japonicum, 8-methoxypsoralen and umbelliferone from Foeniculum vulgare and pomonic acid and jiocerebroside from Rehmanniae glutinosa significantly increased the accumulation of lipid droplets. These results suggest that ethanol extracts of Cirsium japonicum, Carthamus tinctorius, Rehmanniae glutinosa (preparata), Polygala tenuifolia, Foeniculum vulgare, Polygonum multiflorum, and Acorus gramineus and water extracts of Polygonum multiflorum and Rehmanniae glutinosa can cause fatty liver disease by decreasing ${\beta}$-oxidation of fatty acid and increasing lipogenesis.

• Food Science and Biotechnology
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• v.17 no.6
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• pp.1327-1331
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• 2008

In order to determine whether peach contains compounds to regulate adipocyte differentiation, extracts of flesh/pericarp of yellow/white peach were prepared in water, ethyl acetate (EtOAc), or n-butanol solvent and determined for effects on adipocyte differentiation in C3H10T1/2 or 3T3-L1 cells. Interestingly, none of peach extracts has statistically significant stimulatory effect on the adipocyte differentiation in C3H10T1/2. Furthermore, the presence of EtOAc extract of white peach pericarp (WPP) was found to inhibit lipid accumulation in 3T3-L1 cells both by microscopic examination of Oil Red O-stained lipid droplets and by spectrophotometric quantification of extracted stain, indicating a significant inhibitory effect on adipocyte differentiation. The inhibition of lipid accumulation was accompanied by a significant decrease in the expression levels of adipocyte molecular markers-peroxisome proliferator-activated receptor $\gamma$, CAAT enhancer binding protein $\alpha$, and fatty acid-binding protein. Thus, this study determined that WPP EtOAc extract contains the inhibitory compound(s) on adipogenesis.

• Korean Journal of Veterinary Service
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• v.44 no.4
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• pp.195-207
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• 2021

Species A rotaviruses (RVAs) replicate and assemble their immature particles within electron dense compartments known as viroplasms, where lipid droplets (LDs) interact with the viroplasm and facilitate viral replication. Despite the importance of LD formation in the life cycle of RVAs, the upstream molecules modulating LD formation remain unclear. This study aimed to find out the role of sterol regulatory element-binding proteins (SREBPs) in reprogramming of LD formation after RVA infection. Here, we demonstrate that RVA infection reprograms the sterol regulatory element-binding proteins (SREBPs)-dependent lipogenic pathways in virus-infected cells, and that both SREBP-1 and -2 transactivated genes, which are involved in fatty acid and cholesterol biosynthesis, are essential for LD formation. Our results showed that pharmacological inhibition of SREBPs using AM580 and betulin and inhibition of their downstream cholesterol biosynthesis (simvastatin for HMG-CoA reductase) and fatty acid enzymes (TOFA) negatively modulated the intracellular triacylglycerides and cholesterol levels and their resulting LD and viroplasm formations. Interestingly, pharmacological inhibition of SREBPs significantly reduced RVA protein synthesis, genome replication and progeny production. This study identified SREBPs-mediated lipogenic reprogramming in RVA-infected host cells, which facilitates virus replication through LD formation and its interaction with viroplasms, suggesting that SREBPs can be a potential target for the development of efficient and affordable therapeutics against RVA infection.

• Animal Bioscience
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• v.36 no.2
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• pp.295-306
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• 2023

Objective: Inhibiting the p38 mitogen-activated protein kinase (MAPK) signaling pathway delays differentiation and increases proliferation of muscle stem cells in most species. Here, we aimed to investigate the effect of p38 inhibitor (p38i) treatment on the proliferation and differentiation of chicken muscle stem cells. Methods: Chicken muscle stem cells were collected from the muscle tissues of Hy-line Brown chicken embryos at embryonic day 18, then isolated by the preplating method. Cells were cultured for 4 days in growth medium supplemented with dimethyl sulfoxide or 1, 10, 20 μM of p38i, then subcultured for up to 4 passages. Differentiation was induced for 3 days with differentiation medium. Each treatment was replicated 3 times. Results: The proliferation and mRNA expression of paired box 7 gene and myogenic factor 5 gene, as well as the mRNA expression of myogenic differentiation marker gene myogenin were significantly higher in p38i-treated cultures than in control (p<0.05), but immunofluorescence staining and mRNA expression of myosin heavy chain (MHC) were not significantly different between the two groups. Oil red O staining of accumulated lipid droplets in differentiated cell cultures revealed a higher lipid density in p38i-treated cultures than in control; however, the expression of the adipogenic marker gene peroxisome proliferator activated receptor gamma was not significantly different between the two groups. Conclusion: p38 inhibition in chicken muscle stem cells improves cell proliferation, but the effects on myogenic differentiation and lipid accumulation require additional analysis. Further studies are needed on the chicken p38-MAPK pathway to understand the muscle and fat development mechanism.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2023.04a
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• pp.46-46
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• 2023

It has been reported that Rosa acicularis has anti-obesity activity by inhibiting the digestive lipase activity. However, there is a lack of clear in vitro studies regarding the anti-obesity activity of Rosa acicularis. Therefore, in this study, we aimed to verify the anti-obesity activity of Rosa acicularis leaves (RAL) and elucidate its mechanism of action in 3T3-L1 preadipocytes. RAL dose-dependently inhibited the accumulation of lipid droplets and triacylglycerol. RAL had no effect on cell proliferation and survival in undifferentiated 3T3-L1 cells, but it inhibited cell proliferation in differentiating 3T3-L1 cells. RAL increased ATGL, p-HSL, and HSL, and decreased perilipin-1 in differentiating 3T3-L1 cells. In addition, RAL reduced lipid droplet accumulation and increased free glycerol content in differentiated 3T3-L1 cells. RAL increased ATGL and HSL in differentiated 3T3-L1 cells. Also, RAL increased p-AMPK, PPARγ, UCP-1, and PGC-1α in differentiating 3T3-L1 cells. AMPK inhibition by Compound C attenuated RAL-mediated increase of ATGL, HSL, PPARγ, and UCP-1 in 3T3-L1 cells. Taken together, it is thought that RAL may inhibit lipid accumulation through lipolysis and thermogenesis via the activation of AMPK in adipocytes.