• Title/Summary/Keyword: PPAR-${\alpha}$

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Levels of Plasma Glucose and Lipid in Rats Fed Bread Supplemented with Natural Extracts (천연추출물이 첨가된 식빵을 섭취한 흰쥐의 혈당 및 지질수준에 미치는 영향)

  • Kim, Se-Wook;Han, Ah-Ram;Chun, Su-Hyun;Nam, Mi-Hyun;Hong, Chung-Oui;Kim, Bok Hee;Kim, Tae Cheol;Lee, Kwang-Won
    • Korean Journal of Food Science and Technology
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    • v.48 no.1
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    • pp.77-85
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    • 2016
  • In this study, 4-week-old rats were fed bread supplemented with Terminalia chebula (TC), Plantago asiatica (PA), Linder obtusiloba (LO), and Capsosiphon fulvescens (CF) ethanol extracts, to determine the decrease in blood glucose levels, as well as the anti-inflammatory and lipid-enhancing effects. Previous studies have demonstrated the antioxidative effects of these ethanol extracts. After sacrifice, the liver tissue, whole blood, and serum samples were collected for biochemical analysis. The results showed a significant decrease in blood glucose level, lipid peroxidation, malondialdehyde (MDA) level, HbA1c level, total cholesterol, and low-density lipoprotein (LDL)-cholesterol (p<0.05) and an increase in high-density lipoprotein (HDL)-cholesterol level in rats fed bread supplemented with LO and CF ethanol extracts (p<0.05). Therefore, the results of this study demonstrate that bread supplemented with LO and CF ethanol extracts can potentially affect the blood glucose level and lead to lipid enhancement.

Antiadipogenic Activity of Solvent-partitioned Fractions from Limonium tetragonum in 3T3-L1 Preadipocytes (갯질경이 용매분획물의 3T3-L1전지방세포에서의 지방생성억제 효과)

  • Kwon, Myeong Sook;Kim, Jung-Ae;Oh, Jung Hwan;Karadeniz, Fatih;Lee, Jung Im;Seo, Youngwan;Kong, Chang-Suk
    • Journal of Life Science
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    • v.29 no.1
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    • pp.60-68
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    • 2019
  • Limonium tetragonum, an edible halophyte that grows on salt marshes in Korea, is thought to possess various health benefits (e.g., antioxidant, antitumor, and hepatoprotective). In the present study, different solvent partitioned subfractions, water ($H_2O$), buthanol (n-BuOH), 85% aqueous methanol (85% aq. MeOH), and hexane (n-hexane), from crude extract of L. tetragonum were tested for their ability to prevent adipogenesis in differentiating 3T3-L1 preadipocytes. The treatment of differentiating 3T3-L1 preadipocytes with L. tetragonum subfractions (LTFs) resulted in suppressed adipogenesis and reduced expression of adipogenesis-related transcription factors such as peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$), CCAATT/enhancer-binding protein alpha ($C/EBP{\alpha}$), and sterol regulatory element-binding protein 1c (SREBP-1c) at both mRNA and protein levels. In addition, the LTF treatment notably decreased the levels of phosphorylated p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) of the mitogen-activated protein kinase (MAPK) pathway in association with $PPAR{\gamma}$-linked adipogenesis. Among all the tested LTFs, $H_2O$ and n-hexane were the most effective in lowering lipid accumulation and regulating the adipocyte differentiation via $PPAR{\gamma}$ pathway. Taken together, the results indicated that the $H_2O$ and n-hexane LTFs contain bioactive compounds that may exhibit significant antiadipogenesis activity by downregulation of the $PPAR{\gamma}$ pathway and inactivation of the MAPK signal pathway in 3T3-L1 preadipocytes.

PPARα-Target Gene Expression Requires TIS21/BTG2 Gene in Liver of the C57BL/6 Mice under Fasting Condition

  • Hong, Allen Eugene;Ryu, Min Sook;Kim, Seung Jun;Hwang, Seung Yong;Lim, In Kyoung
    • Molecules and Cells
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    • v.41 no.2
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    • pp.140-149
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    • 2018
  • The $TIS21^{/BTG2/PC3}$ gene belongs to the antiproliferative gene (APRO) family and exhibits tumor suppressive activity. However, here we report that TIS21 controls lipid metabolism, rather than cell proliferation, under fasting condition. Using microarray analysis, whole gene expression changes were investigated in liver of TIS21 knockout (TIS21-KO) mice after 20 h fasting and compared with wild type (WT). Peroxisome proliferator-activated receptor alpha ($PPAR{\alpha}$) target gene expression was almost absent in contrast to increased lipid synthesis in the TIS21-KO mice compared to WT mice. Immunohistochemistry with hematoxylin and eosin staining revealed that lipid deposition was focal in the TIS21-KO liver as opposed to the diffuse and homogeneous pattern in the WT liver after 24 h starvation. In addition, cathepsin E expression was over 10 times higher in the TIS21-KO liver than that in the WT, as opposed to the significant reduction of thioltransferase in both adult and fetal livers. At present, we cannot account for the role of cathepsin E. However, downregulation of glutaredoxin 2 thioltransferase expression might affect hypoxic damage in the TIS21-KO liver. We suggest that the $TIS21^{/BTG2}$ gene might be essential to maintain energy metabolism and reducing power in the liver under fasting condition.

Artemisia scoparia Inhibits Adipogenesis in 3T3-L1 Pre-adipocytes by Downregulating the MAPK Pathway (비쑥 추출물이 3T3-L1 지방세포 분화 및 MAPK 신호 전달 경로에 미치는 영향)

  • Oh, Jung Hwan;Karadeniz, Fatih;Seo, Youngwan;Kong, Chang-Suk
    • Journal of Life Science
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    • v.28 no.9
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    • pp.999-1006
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    • 2018
  • Obesity is epidemic worldwide and has reportedly been linked to the progression of several metabolic and cardiovascular diseases. The natural products are decreasing the side effects of medicines used for obesity and also have health benefits dut to their numerous bioactive compounds. In this context, Artemisia scoparia is a widespread plant that has been suggested as possessing various types of bioactivity. In this study, the crude extract from A. scoparia (ASE) was tested for its ability to suppress adipogenesis in mouse 3T3-L1 pre-adipocytes. The molecular pathway by which ASE affects differentiation of 3T3-L1 cells was also investigated. The introduction of ASE to differentiating 3T3-L1 pre-adipocytes resulted in suppressed adipogenesis, as confirmed by decreased intracellular lipid accumulation. The differentiating cells treated with 10 and $100{\mu}g/ml$ of ASE showed 21.9 and 29.0% less lipid accumulation, respectively, than untreated adipocytes. In addition, the results indicated that ASE treatment lowered the expression of the adipogenesis-related factors $PPAR{\gamma}$, $C/EBP{\alpha}$, and SREBP-1c. Furthermore, treating with ASE notably decreased levels of phosphorylated p38, ERK, and JNK in 3T3-L1 adipocytes. These results indicate that ASE exhibits significant anti-adipogenesis activity by downregulating the MAPK and $PPAR{\gamma}$ pathways during the differentiation of 3T3-L1 pre-adipocytes. Therefore, A. scoparia may be a potential source of natural products against obesity.

Skin Hydration and Skin Barrier Effects of Cymbopogon citratus and Perilla frutescens Extracts (레몬그라스와 자소엽 추출물의 피부보습 및 피부장벽에 관한 연구)

  • So, Yangkang;Hwang, Ji Young;Kim, Hyun Woo;Jo, Ha Neul;Lee, Tae-Bum
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.45 no.3
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    • pp.225-235
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    • 2019
  • Cymbopogon citratus (CC) and Perilla frutescens (PF) are known to exert various biological effects. However, their skin hydration and skin barrier effects remain unclear. This study investigated effects of their extracts on skin hydration and skin barrier and analysed the phenolic compounds. effects of these extracts on skin hydration in HaCaT cells showed that Hyaluronic acid production in cells treated with ethanol extracts was higher than that treated with water extracts for both CC and PF. HPLC was used to analyse 19 phenolic compounds in CC and PF ethanol extracts (CCE and PFE). Results revealed chlorogenic acid and p-coumaric acid in CCE and rosmarinic acid and caffeic acid in PFE. Expression levels of hyaluronan synthase 1 (HAS1), HAS2, HAS3, and aquaporin 3 (AQP3), which are related to skin moisturization, and filaggrin and loricrin, which are related to skin barrier were higher in cells treated with CCE than with PFE. CCE and PFE also increased expression of PPAR-a protein involved in skin moisturization and epidermal differentiation in a concentration-dependent manner. As major components of CCE, chlorogenic acid and p-coumaric acid increased PPAR-a protein expression. Thus, CCE and PFE could be used as functional cosmetic materials for skin hydration and skin barrier effects.

Effect of Sasa Borealis and White Lotus Roots and Leaves on Insulin Action and Secretion In Vitro (In vitro에서 조릿대, 연근과 연잎이 인슐린 작용 및 분비에 미치는 영향)

  • Ko, Byoung-Seob;Jun, Dong-Wha;Jang, Jin-Sun;Kim, Ju-Ho;Park, Sun-Min
    • Korean Journal of Food Science and Technology
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    • v.38 no.1
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    • pp.114-120
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    • 2006
  • Anti-diabetic effects of extracts and fractions of Sasa borealis (SB), white lotus roots (LR) and leaves (LL), and their mixture were determined in 3T3-L1 adipocytes and Min6 cells by investigating insulin-sensitizing activity and glucose-stimulated insulin secretion, respectively. SB, LR, LL, and mixture of SB, LR, and LL (3 : 2 : 3) were extracted using 70% ethanol, and m mixture extract was fractionated by XAD-4 column chromatography with serial mixture solvents of methanol and water. Fractional extractions were utilized for anti-diabetic effect assay. SB and LR extracts increased insulin-stimulated glucose uptake, but not as much as mixture of SB, LR, and LL. Significant insulin-sensitizing activities of 20 and 80% methanol fractions of SB, LR, and LL mixture extract were observed in 3T3-L1 adipocytes, giving 0.5 or $5\;{\mu}g/mL$ each fraction with 0.2 nM insulin to attain glucose uptake level similar to that attained by 10 nM insulin alone. Similar to pioglitazone, peroxisome proliferators-activated $receptor-{\gamma}\;(PPAR-{\gamma})$ agonist, 20 and 80% methanol fractions increased adipocytes by stimulating differentiation from fibroblasts and triglyceride synthesis. LL extract and 20, 60, and 80% methanol fractions of the mixture suppressed ${\alpha}-amylase$ activity, but did not modulate insulin secretion capacity of Min6 cells in both low and high glucose media. These data suggest 20 and 80% methanol tractions contain potential insulin sensitizers with functions similar to that of $PPAR-{\gamma}$ agonist. Crude extract of SB, LR, and LL mixture possibly improves glucose utilization by enhancing insulin-stimulated glucose uptake and inhibiting carbohydrate digestion without affecting insulin secretion in vivo.

Mitochondria Control Protein as a Novel Therapeutic Target for Metabolic Syndrome

  • KimPak, Young-Mi
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2008.04a
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    • pp.23-30
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    • 2008
  • Mitochondria biogenesis requires a coordination of two genomes, nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). Disruption of mitochondria function leads to a loss of mitochondrial membrane potential and ATP generating capacity and consequently results in chronic degenerative diseases including insulin resistance, metabolic syndrome and neurodegenerative diseases. Although PPAR-${\gamma}$ coactivator-$1{\alpha}$ (PGC-$1{\alpha}$) was discovered as a central regulator of mitochondria biogenesis and a transcriptional co-activator of nuclear respiratory factor (NRF) and mitochondrial transcription factor A (Tfam), the expressions of PGC-$1{\alpha}$, NRF and Tfam were not significantly altered in tissues showing abnormal mitochondria functions. This observation suggests that there should be another regulator(s) for mitochondria function. Here, we demonstrate microRNAs (miRNAs) can modulate mitochondria function. Overexpression of microRNA dissipated mitochondrial membrane potential and increased ROS production in vitro and in vivo. It will be discussed the target of microRNA and its role in metabolic syndrome.

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Inhibitory Effect of Water Extracts of Aconiti Lateralis Preparata Radix and Acanthopanacis Cortex on Differentiation of Bone Marrow-Derived Adipocytes and Osteoclasts (부자(附子)와 오가피(五加皮) 물 추출물의 골수유래 지방세포와 파골세포 분화 억제 효과)

  • Lee, Kyung-Seon;Choi, Eun-Sik;Han, Sang-Yong;Kim, Yun-Kyung
    • Herbal Formula Science
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    • v.22 no.1
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    • pp.151-165
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    • 2014
  • Objectives : The aim of this study was to evaluate the efficacy of Aconiti Lateralis Preparata Radix (AP) and Acanthopanacis Cortex (AT) extracts in bone-derived adipocyte OP9 cell, osteoclast and osteoblast-like MG63 cells. Methods : MTT assay was used to evaluate the cytotoxicity of AP and AT extracts on OP9, osteoclast and MG63 cells. OP9 cells were treated with AP and AT, and the alterations in fat storage in the cells were determined by the Oil red O. To explain effects of RANKL-induced osteoclast differentiation in bone marrow macrophages, we performed the TRAP staining. The protein level of CAAAT/enhancer binding protein alpha ($C/EBP{\alpha}$) and peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) as a adipocyte differentiation marker, and adiponectin was examined using western blot in differentiated OP9 cells. Effects of related genes were confirmed by luciferase assay using reporter assay. Results : AP and AT was not toxic on OP9 and MG63 cells, but AT was a little cytotoxic to osteoclast at the dose of $100{\mu}g/m{\ell}$. They could inhibit differentiation of OP9 cells and osteoclast with results of oil red O staining and TRAP staining. By western blot, AP and AT decreased the expression of $PPAR{\gamma}$ and $C/EBP{\alpha}$ which is the key transcription factor in adipogenesis and adiponectin secretion. AT also inhibited the BMP-4 activity in luciferase assay. AP also inhibited BMP-4 and Wnt3a activity, stimulated ER-${\beta}$ activity but inhibited androgen receptor activity. Conclusions : These results show AP and AT can be useful in osteoporosis and obesity via inhibition of osteoclast and adipocyte differentiation.

Effects of Fractions from Benincasa hispida on Inhibition of Adipogenesis in 3T3-L1 Preadipocytes (동과 분획물이 3T3-L1 지방세포 분화 억제에 미치는 영향)

  • You, Yang-Hee;Jun, Woo-Jin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.7
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    • pp.895-900
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    • 2012
  • The effects of three fractions, hexane (BHHH), chloroform (BHHC), and ethyl acetate (BHHE), from water extract of Benincasa hispida on the underlying mechanisms of adipogenesis were investigated in 3T3-L1 cells. Intracellular lipid droplets were stained with Oil Red O dye and quantified. Compared to control, lipid accumulation significantly decreased by 11% and 13% upon treatment with BHHC and BHHE, respectively at a concentration of 50 ${\mu}g/mL$. Intracellular triglyceride (TG) levels were also reduced by 21% and 16%, respectively, at the same concentration. To determine the mechanism behind the reductions in TG content and lipid accumulation, glycerol release and expression levels of adipogenic marker genes were measured. The levels of free glycerol released into culture medium increased by 13% and 17% upon treatment with BHHC and BHHE, respectively. In subsequent measurements using real-time polymerization chain reaction, the mRNA levels of $PPAR{\gamma}$, C/$EBP{\alpha}$, and leptin significantly decreased upon treatment with BHHE (45%, 67%, and 35%) in comparison with non-treated control. These results suggest that BHHE inhibits adipocyte differentiation by blocking $PPAR{\gamma}$, C/$EBP{\alpha}$, and leptin gene expression in 3T3-L1 cells, resulting in reduced lipid accumulation, increased glycerol release, and intracellular triglycerides.

Effects of CoCl2 on multi-lineage differentiation of C3H/10T1/2 mesenchymal stem cells

  • Yoo, Hong Il;Moon, Yeon Hee;Kim, Min Seok
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.1
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    • pp.53-62
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    • 2016
  • Mesenchymal stem cells (MSCs) in the bone marrow and other somatic tissues reside in an environment with relative low oxygen tension. Cobalt chloride ($CoCl_2$) can mimic hypoxic conditions through transcriptional changes of some genes including hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) and vascular endothelial growth factor (VEGF). This study evaluated the potential role of $CoCl_2$ preconditioning on multi-lineage differentiation of C3H/10T1/2, a murine MSC line to understand its possible molecular mechanisms in vitro. $CoCl_2$ treatment of MSCs markedly increased HIF-$1{\alpha}$ and VEGF mRNA, and protein expression of HIF-$1{\alpha}$. Temporary preconditioning of MSCs with $CoCl_2$ induced up-regulation of osteogenic markers including alkaline phosphatase, osteocalcin, and type I collagen during osteogenic differentiation, followed by enhanced mineralization. $CoCl_2$ also increased chondrogenic markers including aggrecan, sox9, and type II collagen, and promoted chondrocyte differentiation. $CoCl_2$ suppressed the expression of adipogenic markers including $PPAR{\gamma}$, aP2, and $C/EBP{\alpha}$, and inhibited adipogenesis. Temporary preconditioning with $CoCl_2$ could affect the multi-lineage differentiation of MSCs.