• Journal of Korean Medicine for Obesity Research
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• v.16 no.2
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• pp.109-115
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• 2016

Objectives: The all anti-obesity drugs currently approved by the US Food and Drug Administration work by reducing energy intake. In fact, no approved drug targets energy expenditure. In Korean medicine, it is known to Qi or Yang invigorating therapy could increase energy metabolism. Aconitum carmichaeli Debx (ACD) is a Yang invigorating herb, often used for treat obesity in Korean medicine. In the present study, the authors investigated the regulatory effects of ACD in energy metabolism and mitochondrial biogenesis in C2C12 skeletal muscle cells. Methods: The water extract of ACD (0.2, 0.5 and 1.0 mg/ml) were treated in differentiated C2C12 cells. The protein or mRNA levels of target genes were analyzed and mitochondrial mass were investigated. Results: ACD activated the expressions of peroxisome proliferator-activated receptor gamma coactivator 1-alpha ($PGC-1{\alpha}$), nuclear respiratory factor 1 and TFAM and increased mitochondrial mass. ACD also increased adenosin monophosphate-activated protein kinase (AMPK), and acetyl-CoA carboxylase. Conclusions: This study suggests that ACD has the potential to increase energy metabolism and mitochondrial biogenesis by activating AMPK and $PGC1{\alpha}$.

• Journal of Gastric Cancer
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• v.2 no.2
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• pp.85-90
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• 2002

Purpose: Perforated gastric cancer (PGC) is rare and occurs in $1\∼4\%$ of all gastric cancers. Possible dissemination of tumor cells at the time of perforation of the gastric carcinoma has been a matter of concern. The intraoperative determination of what kind of operation should be done and how extensive the lymphnode dissection should be still remains controversial. The purpose of this study is to evaluate the factors influencing the survival and to determine the optimal treatment for PGC. Materials and Methods: A total of 42 patients were operated on for a perforated gastric carcinoma at Soonchunhyang University Chunan Hospital from 1983 to 2000. the age and the sexes of the patients, the location of perforation, the diameter of perforation, the histologic type of the tumor, the depth of wall invasion, the absence or presence of lymph node metastasis / distant metastasis, the stage of disease, the type of operation, and the outcomes were examined. Statistically significant differences were analyzed by using Fisher's exact test. Results: The stage distributions according to the UICC classification were 1 case of stage I, 6 cases of stage II, 17 cases of stage III, and 11 cases of stage IV. An emergency gastrectomy was done in 26 patients ($61.9\%$), with a 5-yr survival rate of $44\%$. The survival of patients was significantly influenced by the depth of wall invasion, the lymphnode metastasis, distant metastasis, the stage of disease, and the type of operation. Conclusions: an emergency gastrectomy is the treatment of choice for most patients with resectable PGC. Choosing more a optimistic surgical approach for potentially curative cases of PGC should be one way to increase the patient's survival rate.

• Journal of Life Science
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• v.29 no.3
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• pp.303-310
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• 2019

The purpose of the study was to compare the effect of either moderate or high intensity aerobic exercise on inflammasome, M1, M2 macrophage infiltration and brown adipocyte markers in subcutaneous adipose tissue of the high fat diet-induced obese mice. The 4 weeks male C57BL/6 mice were randomly assigned to four groups: normal diet control (NC; n=10), high-fat diet control (HC; n=10), high fat diet with moderate intensity exercise (HME; n=10), or high fat diet with high intensity exercise (HIE; n=10) groups. The high fat diet was given 60% calories from fat whereas normal diet was given 18% calories from fat. The moderate intensity exercise group (HME) was set at 10m/min in the first 2 weeks, 12m/min in 3-5 weeks and 14m/min in 6-16 weeks and the high intensity exercise group (HIE) was set at 14m/min in the first 2 weeks, 17m/min in 3-5 weeks and 18m/min in 6-16 weeks. The semi quantitative reverse transcription-polymerase chain reaction (RT PCR) was used to analyze the gene expression. The moderate intensity exercise significantly reduced the expression of NLRP3, F480, CD11c and CD86. Further, the moderate intensity exercise significantly increased CD206 and $PGC1{\alpha}$, BMP7 and PRDM. The high intensity exercise significantly reduced NLRP3, CD11c and CD86. Further, the high intensity exercise significantly increased $PGC1{\alpha}$ and BMP7. In conclusion, moderate intensity exercise has more positive effects on inflammasome, M1, M2 macrophage infiltration and brown adipocyte maskers compared to high intensity exercise in high fat diet induced obese mice.

• Molecules and Cells
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• v.38 no.4
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• pp.343-348
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• 2015

Fiber type-specific programs controlled by the transcription factor MEF2 dictate muscle functionality. Here, we show that HDAC4, a potent MEF2 inhibitor, is predominantly localized to the nuclei in fast/glycolytic fibers in contrast to the sarcoplasm in slow/oxidative fibers. The cytoplasmic localization is associated with HDAC4 hyper-phosphorylation in slow/oxidative-fibers. Genetic reprogramming of fast/glycolytic fibers to oxidative fibers by active CaMKII or calcineurin leads to increased HDAC4 phosphorylation, HDAC4 nuclear export, and an increase in markers associated with oxidative fibers. Indeed, HDAC4 represses the MEF2-dependent, PGC-$1{\alpha}$-mediated oxidative metabolic gene program. Thus differential phosphorylation and localization of HDAC4 contributes to establishing fiber type-specific transcriptional programs.

• Journal of Korean Medicine for Obesity Research
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• v.23 no.2
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• pp.60-68
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• 2023

Objectives: This study was conducted to compare the effects of Hominis placenta (Jahage, J) and wild ginseng (SanSam, S) pharmacopuncture drugs on muscle differentiation and energy metabolism regulation in C2C12 myotubes. Methods: The C2C12 myoblasts were differentiated into myotubes for 5 days by replacing in medium containing 2% horse serum and then treated with J and S pharmacopuncture extract at different concentrations for 24 hr. The expression of myosin heavy chain and energy metabolism-regulating factors, myosin heavy chain (MHC), nuclear respiratory factor-1 (NRF-1), and proliferator-activated receptor γ coactivator-1 alpha (PGC-1α) were determined in C2C12 myotubes by western blot. Additionally, the phosphorylation of AMPK and the expression of mitochondrial biogenesis, including sirtuin 1 (SIRT1) were determined in the myotubes. Results: As a result, treatment with J and S pharmacopuncture extract at 0.1 and 1 mg/mL increased the MHC expression in C2C12 myotubes compared with non-treated cells, but only S pharmacopuncture was shown a significant and distinct increase in the expression. Expression of TFAM and NRF-1 was also shown significant increases in S and J pharmacopuncture in C2C12 myotubes compared to non-treated cells. The phosphorylation of AMPK and the expression of PGC-1α and SIRT1 showed increased expression in S and J pharmacopuncture compared to non-treated cells. The effect of low-dose of J pharmacopuncture on the phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and PGC-1α expression was greater than that of S pharmacopuncture. Conclusions: In conclusion, both J and S pharmacopuncture promote muscle differentiation in C2C12 myoblasts into myotubes and energy metabolism through the AMPK/SIRT1 signaling pathway. This indicates that the pharmacopuncture with tonic herbal medicines can help to improve skeletal muscle function.

• Korean Journal of Food Science and Technology
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• v.49 no.2
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• pp.192-202
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• 2017

In this study, factors involved in lipid and energy metabolism following treatment with ethanolic extract of the Polygonatum sibiricum rhizome (ID1216) were evaluated in high-fat diet-induced obese mice. ID1216-treated mice showed a significant reduction in weight gain compared to non-treated mice. ID1216 treatment increased the protein levels of AMP-dependent protein kinase, sirtuin1, peroxisome proliferator-activated receptor ${\gamma}$ coactivator 1-${\alpha}$ ($PGC1{\alpha}$), peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) and uncoupling proteins in the adipose tissue, liver and muscle compared to vehicle treatment. Analysis of downstream signals of the sirtuin1 $PGC1{\alpha}$-$PPAR{\alpha}$ pathway showed that ID1216 regulates the expression of ${\beta}$-oxidation related genes such as acyl-CoA oxidase, carnitine palmitoyltransferase1, acyl-CoA dehydrogenase and adipocyte protein 2. In addition, ID1216 increased the expression of adipose triglyceride lipase. These results suggest that ID1216 has anti-obesity effects by regulating the genes involved thermogenesis, ${\beta}$-oxidation and lipolysis in a diet-induced obesity model.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.262.1-262.1
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• 2002

Uncoupling proteins (UCPs) are transmembrane proton transporters present in the mitochondria. In UCPs. UCP1 and UCP3 play an important role in adaptive thermogenesis by uncoupling mitochondrial oxidation of substrates from ATP synthesis. PPARg coactivator 1(PGC-1) regulates transcriptional activity of PPARg and other nuclear receptors and controls the expression of UCPs. (omitted)

• Korean Journal of Poultry Science
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• v.41 no.4
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• pp.261-270
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• 2014

This study was conducted to establish the method for preserving chicken primordial germ cells (PGCs) that enables long-term storage in liquid nitrogen ($LN_2$) for developmental engineering or preservation of species. The purpose of this study is to clarify the effects of simple freeze-thaw treatment on viability of PGCs in chickens and to the optimal protocol for PGCs freezing. PGCs obtained from the germinal gonade of an early embryos of 5.5~6 day (stage 28) of Isa Brown, Korean Ogye (KO), White Leghorn and Commercial breeds, using the MACS method were suspended in a freezing medium containing a freezing and protecting agents (e.g. dimethyl sulfoxide (DMSO), ethylene glycol (EG) and propylene glycol (PG)). The gonadal cells, including PGCs, were then frozen in 1 of the following cryoprotectant treatments : 2.5%, 5%, 10%, 15%, and 0% cryoprotectant (DMSO, EG, PG) as a control. Effects of exposure to simple freezing, with different concentrations of the cryoprotectant solution, were examined. After simple freezing, the viability of PGCs after freeze-thawing was significantly higher for Commercial breeds ($88.7{\pm}2.4%$) than KO ($85.1{\pm}0.4%$), Isa Brown ($84.6{\pm}0.2%$) and White Leghorn ($85.9{\pm}0.1%$) (p<0.05) using 10% EG cryoprotectant. Therefore, these systems may contribute in the improvement of cryopreservation for a scarce species in birds preservation. This study established a method for preserving chicken PGCs that enables systematic storage and labeling of cryopreserved PGCs in liquid ($LN_2$) at a germplasm repository and ease of entry into a database.

• Journal of the Korean Institute of Oriental Medical Informatics
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• v.21 no.1
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• pp.14-22
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• 2015

Flavonoids show diverse bioactivities, such as anti-oxidant, anti-cancer, anti-allergic, anti-inflammatory, and anti-viral. Quercetin is one of the flavonoids present in a wide range of plants, especially onions and consumed all over the world. Recently, it is known that quercetin induces mitochondrial biogenesis in vivo and in vitro. However, detail mechanism of these actions remains unknown. We investigated quercetin's effects on mitochondrial biogenesis in HepG2 cells, and determined the mechanisms involved. We found that quercetin treatment induced the expression of mitochondrial biogenesis activators, $PGC-1{\alpha}$, NRF-1, TFAM, and mitochondrial proteins, cytochorome c and complex IV (COXIV). Moreover, amount of mitochondrial DNA was also increased by quercetin. Quercetin has been known to induce heme oxygenase (HO)-1 in several types of cells. Here, we found quercetin induces HO-1, and inhibition of HO-1 or CO, which is product of HO-1, decreased quercetin-induced mitochondrial biogenesis such as induction of $PGC-1{\alpha}$, NRF-1, TFAM, cytochorome c, COXIV, and mitochondrial DNA. These findings imply that quercetin can increase mitochondrial biogenesis via HO-1/CO system. High glucose results in dysfunction of mitochondria biogenesis. In the present study, 25 mM glucose decreased mitochondrial biogenesis and this damage was restored by quercetin. Conversely, inhibition of HO-1 or CO inhibited quercetin-induced mitochondrial biogenesis rescue. These results suggest that quercetin enhances mitochondrial biogenesis via HO-1/CO system and hence, can rescue mitochondria from damage by high glucose.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.2
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• pp.201-211
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• 2016

Although the antioxidant and cardioprotective effects of NecroX-5 on various in vitro and in vivo models have been demonstrated, the action of this compound on the mitochondrial oxidative phosphorylation system remains unclear. Here we verify the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity during hypoxia-reoxygenation (HR). Necrox-5 treatment ($10{\mu}M$) and non-treatment were employed on isolated rat hearts during hypoxia/reoxygenation treatment using an ex vivo Langendorff system. Proteomic analysis was performed using liquid chromatography-mass spectrometry (LC-MS) and non-labeling peptide count protein quantification. Real-time PCR, western blot, citrate synthases and mitochondrial complex activity assays were then performed to assess heart function. Treatment with NecroX-5 during hypoxia significantly preserved electron transport chain proteins involved in oxidative phosphorylation and metabolic functions. NecroX-5 also improved mitochondrial complex I, II, and V function. Additionally, markedly higher peroxisome proliferator-activated receptor-gamma coactivator-$1{\alpha}$ ($PGC1{\alpha}$) expression levels were observed in NecroX-5-treated rat hearts. These novel results provide convincing evidence for the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity and in preserving $PGC1{\alpha}$ during cardiac HR injuries.