• Title/Summary/Keyword: PGC-1

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The Role of Mitochondrial Biogenesis Dysfunction in Diabetic Cardiomyopathy

  • Tao, Li-Chan;Wang, Ting-ting;Zheng, Lu;Hua, Fei;Li, Jian-Jun
    • Biomolecules & Therapeutics
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    • v.30 no.5
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    • pp.399-408
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    • 2022
  • Diabetic cardiomyopathy (DCM) is described as abnormalities of myocardial structure and function in diabetic patients without other well-established cardiovascular factors. Although multiple pathological mechanisms involving in this unique myocardial disorder, mitochondrial dysfunction may play an important role in its development of DCM. Recently, considerable progresses have suggested that mitochondrial biogenesis is a tightly controlled process initiating mitochondrial generation and maintaining mitochondrial function, appears to be associated with DCM. Nonetheless, an outlook on the mechanisms and clinical relevance of dysfunction in mitochondrial biogenesis among patients with DCM is not completely understood. In this review, hence, we will summarize the role of mitochondrial biogenesis dysfunction in the development of DCM, especially the molecular underlying mechanism concerning the signaling pathways beyond the stimulation and inhibition of mitochondrial biogenesis. Additionally, the evaluations and potential therapeutic strategies regarding mitochondrial biogenesis dysfunction in DCM is also presented.

The effects of Allomyrina dichotoma larval extract on palmitate-induced insulin resistance in skeletal muscle cells (장수풍뎅이 유충 추출물이 고지방산 처리 골격근세포의 인슐린 저항성에 미치는 영향)

  • Kim, Kyong;Sim, Mi-Seong;Kwak, Min-Kyu;Jang, Se-Eun;Oh, Yoon Sin
    • Journal of Nutrition and Health
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    • v.55 no.4
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    • pp.462-475
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    • 2022
  • Purpose: Allomyrina dichotoma larvae are one of the approved edible insects with nutritional value and various functional and medicinal properties. Previously we have demonstrated that the Allomyrina dichotoma larval extract (ADLE) ameliorates hepatic insulin resistance in high-fat diet (HFD)-induced diabetic mice through the activation of adenosine monophosphate-activated protein kinase (AMPK). This study investigated the effects of ADLE on insulin resistance in the skeletal muscle and explored mechanisms for enhancing the glucose uptake in palmitate (PAL)-treated C2C12 myotubes. Methods: To induce insulin resistance, the differentiated C2C12 myotubes were treated with PAL (0.5 mM) for 24 hours, and then treated with a 0.5 mg/ml concentration of ADLE, and the resultant effects were measured. The expression levels of glucose transporter-4 (GLUT4), AMPK, and the mitochondrial metabolism-related proteins were analyzed by western blotting. The mRNA expression levels of lipogenesis- related genes were determined by quantitative reverse-transcriptase PCR. Results: The exposure of C2C12 myotubes to 0.5 mg/ml of ADLE increased cell viability significantly compared to PAL-treated cells. ADLE upregulated the protein expression of GLUT4 and enhanced glucose uptake in the PAL-treated cells. ADLE increased the phosphorylated AMPK in both the PAL-treated C2C12 myotubes and HFD-treated skeletal muscle. The reduced expression levels of peroxisome-proliferator-activated receptor gamma co-activator-1 alpha (PGC1α) and uncoupling protein 3 (UCP3) due to the PAL and HFD treatment were reversed by the ADLE treatment. The citrate synthase activity was also significantly increased with the PAL and ADLE co-treatment. Moreover, the mRNA and protein expressions of fatty acid synthesis-related factors were reduced in the PAL and HFD-treated muscle cells, and this effect was significantly attenuated by the ADLE treatment. Conclusion: ADLE activates AMPK, which in turn induces mitochondrial metabolism and reduces fatty acid synthesis in C2C12 myotubes. Therefore, ADLE could be useful for preventing or treating insulin resistance of skeletal muscles in diabetes.

Far-infrared rays enhance mitochondrial biogenesis and GLUT3 expression under low glucose conditions in rat skeletal muscle cells

  • Seo, Yelim;Kim, Young-Won;Lee, Donghee;Kim, Donghyeon;Kim, Kyoungseo;Kim, Taewoo;Baek, Changyeob;Lee, Yerim;Lee, Junhyeok;Lee, Hosung;Jang, Geonwoo;Jeong, Wonyeong;Choi, Junho;Hwang, Doegeun;Suh, Jung Soo;Kim, Sun-Woo;Kim, Hyoung Kyu;Han, Jin;Bang, Hyoweon;Kim, Jung-Ha;Zhou, Tong;Ko, Jae-Hong
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.2
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    • pp.167-175
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    • 2021
  • Far-infrared rays (FIR) are known to have various effects on atoms and molecular structures within cells owing to their radiation and vibration frequencies. The present study examined the effects of FIR on gene expression related to glucose transport through microarray analysis in rat skeletal muscle cells, as well as on mitochondrial biogenesis, at high and low glucose conditions. FIR were emitted from a bio-active material coated fabric (BMCF). L6 cells were treated with 30% BMCF for 24 h in medium containing 25 or 5.5 mM glucose, and changes in the expression of glucose transporter genes were determined. The expression of GLUT3 (Slc2a3) increased 2.0-fold (p < 0.05) under 5.5 mM glucose and 30% BMCF. In addition, mitochondrial oxygen consumption and membrane potential (ΔΨm) increased 1.5- and 3.4-fold (p < 0.05 and p < 0.001), respectively, but no significant change in expression of Pgc-1a, a regulator of mitochondrial biogenesis, was observed in 24 h. To analyze the relationship between GLUT3 expression and mitochondrial biogenesis under FIR, GLUT3 was down-modulated by siRNA for 72 h. As a result, the ΔΨm of the GLUT3 siRNA-treated cells increased 3.0-fold (p < 0.001), whereas that of the control group increased 4.6-fold (p < 0.001). Moreover, Pgc-1a expression increased upon 30% BMCF treatment for 72 h; an effect that was more pronounced in the presence of GLUT3. These results suggest that FIR may hold therapeutic potential for improving glucose metabolism and mitochondrial function in metabolic diseases associated with insufficient glucose supply, such as type 2 diabetes.

Hibiscus manihot leaves Attenuate Accumulation of Lipid Droplets by Activating Lipolysis, Browning and Autophagy, and Inhibiting Proliferation of 3T3-L1 Cells

  • Na Gyeong Geum;Jeong Won Choi;Hyeok Jin Choi;Gwang Hyeon Ryu;Jin Boo Jeong
    • Korean Journal of Plant Resources
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    • v.36 no.6
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    • pp.541-548
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    • 2023
  • In the present study, the effects of HML on lipolysis, adipocyte browning, autophagy, and proliferation were investigated. HML affected lipolysis by increasing the protein levels of ATGL and HSL, and phosphorylation levels of HSL and AMPK. Furthermore, HSL decreased the perilipin-1 levels. In addition, free glycerol content was increased by HML treatment. HML affected adipocyte browning by increasing the protein levels of UCP-1, PGC-1α, and PRDM16. In addition, HML affected autophagy by increasing the levels of LC3-I and LC3-II, and decreasing those of SQSTM1/p62. Moreover, HML affected adipocyte proliferation by suppressing the proliferation of 3T3-L1 cells due to arrest of the cell cycle via blocking the expression of β-catenin and cyclin D1. These results suggest that HML induces lipolysis, adipocyte browning, autophagy, and inhibits excessive proliferation of adipocytes.

The effects of Pueraria lobata extract on gene expression in liver tissue of rat with estrogen-deficient obesity (갈근이 비만 랫드 간조직의 비만관련 유전자 발현에 미치는 영향)

  • Shin, Yoon Sang;Hwang, Gwi Seo
    • Journal of Society of Preventive Korean Medicine
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    • v.18 no.3
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    • pp.117-128
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    • 2014
  • Objective : It is known that Pueriaria lobata has an anti-osteoporetic effect, anti-cancer effect, anti-pyretic effect, and anti-diabetic effect. The aim of this study was to evaluate anti-obesity effect of Pueriaria lobata extract (PLE), and elucidate the effect of it on gene expression related to lipid metabolism. Method : The experiments were performed with the use of ovariectomized rats as estrogen-deficient obesity model. They were grouped NC (normal control), OC (estrogen-deficient control), PLH (100mg/kg of PLE), PLL (20mg/kg). PLE was orally administered for 6 weeks. Body weights and serum lipid level were estimated, and real-time PCR was performed to investigate the effect of PLE on gene expression in liver. Results : PLE decreased the body weight and serum cholesterol and triglyceride, but increased HDL-cholesterol. And PLE increased leptin, CYP27, CPT1, CYP8B1, ACAT2, LDLR, and SCD1, but reduced $PPAR{\gamma}$, PGC1A, HMG-CoA-R, ACAT1, SCD1, and APoB gene expression in liver tissue of rat with estrogen-deficient obesity. Conclusion : It is concluded that Pueriaria lobata reduced body weight, and its effect was expressed by regulation of gene expression related to lipid metabolism in rats with estrogen-deficient obesity.

Effects of resveratrol on laminar shear stress-induced mitochondrial biogenesis in human vascular endothelial cells

  • Kim, Ji-Seok;Park, Joon-Young
    • Korean Journal of Exercise Nutrition
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    • v.23 no.1
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    • pp.7-12
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    • 2019
  • [Purpose] The purpose of the study was to determine the combined effects of resveratrol supplementation with high-flow LSS on mitochondrial biogenesis in human vascular endothelial cells. [Methods] Cultured human umbilical vein endothelial cells were treated with 20 μM of RSV. For the shear experiments, cells grown to a >90% confluence were exposed to physiological levels of LSS (5 to 20 dyne/cm2) for 12 to 36 hours using a cone and plate shear apparatus. Gene expressions were analyzed by western blotting. [Results] Depletion of mitochondrial integrity was directly associated with increase in endothelial activation/dysfunction. The expressions of mitochondrial biogenesis regulator genes, such as SIRT1, PGC-1α, and TFAM, and the mitochondrial contents were significantly increased after treatment with both resveratrol and high-flow LSS for 12 hours. However, supplementation of resveratrol to high-flow LSS for a prolonged duration had no synergistic effect on the levels of mitochondrial biogenesis regulator gene expressions and mitochondrial content compared to the LSS treatment alone. [Conclusion] The present study demonstrated that the supplementation of resveratrol to high-flow LSS has no synergistic effects on enhancing mitochondrial integrity in human vascular endothelial cells.

Effects of Pueraria lobata on Body Weight and Gene Expression in Obese Rats Muscle with Estrogen Deficiency (갈근 추출물이 난소 적출로 비만이 유발된 Rat의 체중 변화와 유전자 발현에 미치는 영향)

  • Shin, Hee-Jong;Yoo, Jeong-Eun;Jung, Eun-Hye;Yoo, Dong-Youl
    • The Journal of Korean Obstetrics and Gynecology
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    • v.25 no.3
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    • pp.71-84
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    • 2012
  • Objectives: GG is the EtOH fraction of extract of Pueraria lobata. In this study, we aimed to elucidate a possibility that GG reduce obesity and obesity-derived complications such as cardiovascular and metabolic disease. Methods: The effects of GG on the estrogen-deficient obese rats and the level of gene expression in muscle of rats were investigated. Results: GG decreased body weight in obese rats with estrogen deficiency. GG increased leptin gene expression in obese rats with estrogen deficiency. GG decreased TNFa gene expression in obese rats with estrogen deficiency. And GG increased PPAR-gamma, PGC-1a, Prdx6, FDFT1, and ACC gene expression of those in obese rats. Conclusions: We conclude GG might reduce body weight and regulate gene expression of muscle in obese rats.

A Survey of Globular Cluster Systems of Massive Compact Elliptical Galaxies in the Local Universe

  • Kang, Jisu;Lee, Myung Gyoon
    • The Bulletin of The Korean Astronomical Society
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    • v.45 no.1
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    • pp.32.2-32.2
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    • 2020
  • Massive Compact Elliptical Galaxies (MCEGs) found in the local universe are as massive as normal galaxies but extremely compact (M∗ > 1011 Msun, Reff < 1.5 kpc). They are considered to be the relics of red nugget galaxies found at high redshift. They are not likely to have undergone many mergers, keeping their original mass and size. Moreover, it is expected that they host a dominant population of red (metal-rich) globular clusters rather than blue (metal-poor) ones. Indeed, Beasley et al. (2018) found that the color distribution of the cluster system of NGC 1277 is unimodal, showing only a red population. However, NGC 1277 is the only case whose cluster system was studied among MCEGs. In this study, we investigate globular cluster systems of 14 nearby MCEGs with a homogeneous data set of HST/WFC3 F814W/F160W archive images. We detect tens to hundreds of globular clusters in each galaxy and examine their color distributions. Surprisingly, the fractions of red globular clusters are similar to those of normal galaxies, and are much lower than that of NGC 1277. We additionally obtain Gemini/GMOS-N g'r'i' images of PGC 70520, one of the 14 nearby MCEGs, to detect more globular clusters from deeper and wider images. We will discuss the results from the Gemini data combined with the results from the HST data in relation with the formation of MCEGs.

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Derivation of primordial germ cells from chicken blastodermal cells by BMP-2 and BMP-4 signaling

  • Kim, Duk-Kyung;Song, Ki-Duk;Lee, Young-Mok;Seo, Sam-Youl;Han, Jae-Yong
    • Proceedings of the Korea Society of Poultry Science Conference
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    • 2002.11a
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    • pp.96-97
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    • 2002
  • Primordial germ cells (PGCs) are the progenitors of the sperms or eggs of adult. Evidence suggests that the specification of primordial germ cells (PGCs) in the mammalian embryo does not depend on maternal determinants. Recent previous studies in the mouse has shown that several bone morphogenetic proteins (BMPs) are required for the formation of PGCs. However, there is no study about the effect of BMPs on avian PGCs. Here, we studied the effects of recombinant human BMP-2 (rhBMP-2) and recombinant human BMP-4 (rhBMP-4) on chicken blastodermal cells in culture. As a results, the addition of rhBMP-2 and rhBMP-4 increased the number of SSEA-1 positive cells in dose-dependent manner. However, there is no synergic effect by using both rhBMP-2 and rhBMP-4.

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T0901317 as an Inhibitor of Transcriptional Activation of Constitutive Androstane Receptor (CAR) (Constitutive androstane receptor (CAR)의 전사활성 저해제로서의 T0901317)

  • Kim, Hyun-Ha;Seol, Won-Gi
    • Journal of Life Science
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    • v.21 no.4
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    • pp.481-485
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    • 2011
  • T0901317 is a potent synthetic ligand for liver X receptor (LXR, NR1H2/3), a member of the nuclear receptor superfamily that functions as a transcription factor. However, T0901317 has been also reported to modulate the activity at least four other nuclear receptors (NRs), acting as agonists for farnesoid X receptor (FXR, NR1H4) and pregnane X receptor (PXR, NR1I2) and as antagonists for androgen receptor (AR, NR3C4) and retinoid-related orphan receptor-${\alpha}$ (ROR-${\alpha}$, NR1F1). We report here that T0901317 can also function as an inhibitor for constitutive androstane receptor (CAR, NR1I3). Since CAR is a major player of xenobiotic and cholesterol metabolism in the liver, along with PXR, FXR and LXR, which are reported to be regulated by T0901317, this further complicates the interpretation of potential results with T0901317 in liver cells.