• 한방비만학회지
• /
• 제16권2호
• /
• pp.109-115
• /
• 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
• /
• 제2권2호
• /
• pp.85-90
• /
• 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.

• 생명과학회지
• /
• 제29권3호
• /
• pp.303-310
• /
• 2019

비만은 체내 과도한 지방 축적으로 인하여 지방세포 자체에서 염증성 사이토카인이 증가로 인하여 세포의 기능을 약화시킨다. 규칙적인 운동은 지방분해와 갈색지방 증가로 인해 비만의 치료방법 중 핵심 전략으로 적용되고 있다. 고강도 운동은 염증성 사이토카인과 근형질세망 스트레스 발생을 초래하여 지방대사에 부정적인 결과를 초래하는 것으로 알려져 있다. 그러나 비만모델에서 중강도 운동과 고강도 운동에 의한 인플라마좀, 대식세포 침윤, 갈색지방 관련 바이오 마커의 비교연구는 이루어진 바 없다. 따라서 이 연구의 목적은 중강도 유산소 운동과 고강도 운동을 비교하여 인플라마좀(NLRP3, ASC), 대식세포 침윤인자 M1 (CD11c, CD86), M2 (CD206), 갈색지방($PGC1{\alpha}$, BMP7, PRDM, UCP1) 관련 변인에 우선적인 효과가 있는지 비교분석하고자 하였다. 이 연구의 목적을 위해 1) 정상식이 그룹(normal diet control, NC; n=10), 2) 60% 고지방식이 그룹(high-fat diet control, HC; n=10), 3) 중강도 운동 그룹(high fat diet with moderate intensity exercise, HME; n=10), 4) 고강도 운동그룹(high fat diet with high intensity exercise, HIE; n=10)으로 나누어 실시하였다. 중강도 운동 그룹은 고지방식이 그룹과 비교하여 NLRP3, F480, CD11c, CD8의 발현이 유의하게 낮아졌다. 중강도 운동은 CD206, $PGC1{\alpha}$, BMP7, PRDM이 유의하게 증가하였다. 고강도 운동은 NLRP3, CD11c and CD86은 유의하게 감소한것으로 확인되었다. 그러나 고강도 운동은 $PGC1{\alpha}$, BMP7는 증가한다. 이러한 결과는 중강도 운동은 인플라마좀, 대식세포 M1, M2 침윤과 갈색지방 세포 관련 요인의 개선이 효과적인 것으로 나타났다.

• Molecules and Cells
• /
• 제38권4호
• /
• pp.343-348
• /
• 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.

• 한방비만학회지
• /
• 제23권2호
• /
• pp.60-68
• /
• 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.

• 한국식품과학회지
• /
• 제49권2호
• /
• pp.192-202
• /
• 2017

황정 주정 추출물 ID1216의 고지방 식이 유도 비만 마우스에서의 체중 증가 억제 효과에 대한 분자생물학적 기전을 확인하고자 단백질과 mRNA 수준에서 지질 및 에너지 대사 관련 유전자들의 발현 변화를 관찰하였다. 본 연구에서 확인된 지표들 간의 상호 작용 및 ID1216의 조절 여부에 관해 Fig. 10에 나타내었다. 실험 결과 ID1216은 고지방 식이 유도 비만 마우스에서 체중 증가 억제를 나타내었으며, 비만 대사 관련 pathway의 상위 유전자로 사료되는 SIRT1과 AMPK의 발현을 조절하는 것으로 나타났다. 활성화된 SIRT1과 AMPK는 $PGC1{\alpha}$의 활성화에 관여하고, 이를 통해 열 발산 대사와 관련된 UCP 단백질과 핵 수용체 단백질인 $PPAR{\alpha}$의 발현이 백색지방, 갈색지방, 간 및 근육에서 증가되는 것이 확인되었다. 각 조직 별로 RT-PCR을 진행한 결과에서는 $PPAR{\alpha}$의 하위 유전자인 aP2, ACO, Acadl, Acadm, CPT1a, CPT1b의 mRNA 발현 수준을 향상시켜 주어 ID1216이 지방산 산화 대사인 ${\beta}$-oxidation의 활성화에 기여할 가능성을 보여주었다. 이와는 별개로 ID1216은 중성지질을 분해하는 것으로 알려진 ATGL의 mRNA 발현 또한 증가시키는 것으로 확인되었다. 본 연구를 통해 ID1216이 조직에 따라 지질 및 에너지 대사와 관련된 인자의 발현에 영향을 주는 체중 조절에 효과적인 소재임을 알 수 있었다. 또한 비만 치료제와의 기전적 차별성과 생약 특유의 섭취 안전성을 특징으로 하는 체중 또는 체지방 조절 기능성 소재로의 활용 가능성도 충분히 가지고 있음을 확인할 수 있었다.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
• /
• pp.262.1-262.1
• /
• 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)

• 한국가금학회지
• /
• 제41권4호
• /
• pp.261-270
• /
• 2014

동결 닭 PGCs의 생식계열 키메라를 이용한 생체에의 복원을 실용화 하기 위해서는, 닭 PGCs의 동결 보존 기술의 향상에 의해 동결 및 융해 후의 많은 생존 세포를 확보하는 것과, 생식계열 키메라의 제작 효율을 높이는 것이 반드시 필요하다. 닭 PGCs는 배양 5.5~6일령의 닭 원시 생식선으로부터 채취하고, MACS 방법에 의해서 순수 닭 PGCs를 분리했다. 15% 각각의 EG와 DMSO를 동결 보호제로 사용한 처리군이 각 군의 농도에 상관없이 유의적(p<0.05)으로 PG 처리군보다 동결 및 융해 후의 세포의 생존율이 높음을 확인하였다. 특히, 10% EG+FBS 조합의 처리군에서 상업용 닭인 한협육종협회3호종(B : 88.7%)이 오계종(A : 85.1%), 아사 브라운종(C : 84.6%) 그리고 화이트 레그혼종(D : 85.9%)의 세 품종보다 동결 및 융해 후의 닭 PGCs의 생존율이 유의적(p<0.05)으로 높음을 확인하였다. 간이 동결에 있어서 가장 높은 생존율을 보인 10% EG이 10% DMSO와 함께 최적의 동결 보호제로서 사용 가능성을 확인하였다.

• 대한한의정보학회지
• /
• 제21권1호
• /
• pp.14-22
• /
• 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
• /
• 제20권2호
• /
• pp.201-211
• /
• 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.