• Journal of Animal Science and Technology
• /
• 제64권6호
• /
• pp.1199-1214
• /
• 2022

Apolipoprotein H (APOH) primarily engages in fat metabolism and inflammatory disease response. This study aimed to investigate the effects of APOH on fat synthesis in duck myoblasts (CS2s) by APOH overexpression and knockdown. CS2s overexpressing APOH showed enhanced triglyceride (TG) and cholesterol (CHOL) contents and elevated the mRNA and protein expression of AKT serine/threonine kinase 1 (AKT1), ELOVL fatty acid elongase 6 (ELOVL6), and acetyl-CoA carboxylase 1 (ACC1) while reducing the expression of protein kinase AMP-activated catalytic subunit alpha 1 (AMPK), peroxisome proliferator activated receptor gamma (PPARG), acyl-CoA synthetase long chain family member 1 (ACSL1), and lipoprotein lipase (LPL). The results showed that knockdown of APOH in CS2s reduced the content of TG and CHOL, reduced the expression of ACC1, ELOVL6, and AKT1, and increased the gene and protein expression of PPARG, LPL, ACSL1, and AMPK. Our results showed that APOH affected lipid deposition in myoblasts by inhibiting fatty acid beta-oxidation and promoting fatty acid biosynthesis by regulating the expression of the AKT/AMPK pathway. This study provides the necessary basic information for the role of APOH in fat accumulation in duck myoblasts for the first time and enables researchers to study the genes related to fat deposition in meat ducks in a new direction.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권6호
• /
• pp.3631-3634
• /
• 2013

MicroRNAs (MiRNAs) play important roles in coordinating a variety of cellular processes and abnormal expression has been linked to the occurrence of several cancers. The miRNA miR-451 is downregulated in colorectal carcinoma (CRC) cells, suggested by several research groups including our own. In this study, synthetic miR-451 mimics were transfected into the SW620 human CRC cell line using Lipofectamine 2000 and expression of miR-451 was analyzed by real time PCR, while expression of CAB39, LKB1, AMPK, AKT, PI3K and Bcl2 was analyzed by Western blot, and cell growth was detected by MTT assay. In comparison to the controls, a significant increase in the expression of miR-451 was associated with significantly decreased expression of CAB39, LKB1, AMPK, AKT, PI3K and Bcl2. The capacity of cell proliferation was significantly decreased by miR-451 expression, which also inhibited cell growth. Our study confirmed that miR-451 has a repressive role in CRC cells by inhibiting cell growth through down-regulating the P13K/AKT pathway.

• BMB Reports
• /
• 제51권9호
• /
• pp.425-426
• /
• 2018

As highly conserved signaling cascades of multicellular organisms, Wnt and Hippo pathways control a wide range of cellular activities, including cell adhesion, fate determination, cell cycle, motility, polarity, and metabolism. Dysregulation of those pathways are implicated in many human diseases, including cancer. Similarly to ${\beta}-catenin$ in the Wnt pathway, the YAP transcription co-activator is a major player in Hippo. Although the intracellular dynamics of YAP are well-known to largely depend on phosphorylation by LATS and AMPK kinases, the molecular effector of YAP cytosolic translocation remains unidentified. Recently, we reported that the Dishevelled (DVL), a key scaffolding protein between canonical and non-canonical Wnt pathway, is responsible for nuclear export of phosphorylated YAP. The DVL is also required for YAP intracellular trafficking induced by E-cadherin, ${\alpha}-catenin$, or metabolic stress. Note that the p53/LATS2 and LKB1/AMPK tumor suppressor axes, commonly inactivated in human cancer, govern the reciprocal inhibition between DVL and YAP. Conversely, loss of the tumor suppressor allows co-activation of YAP and Wnt independent of epithelial polarity or contact inhibition in human cancer. These observations provide novel mechanistic insight into (1) a tight molecular connection merging the Wnt and Hippo pathways, and (2) the importance of tumor suppressor contexts with respect to controlled proliferation and epithelial polarity regulated by cell adhesion.

• Journal of Ginseng Research
• /
• 제46권2호
• /
• pp.235-247
• /
• 2022

Background: Ginsenoside Rg3 is one of the main active ingredients in ginseng. Here, we aimed to confirm its protective effect on the heart function in transverse aortic coarctation (TAC)-induced heart failure mice and explore the potential molecular mechanisms involved. Methods: The effects of ginsenoside Rg3 on heart and mitochondrial function were investigated by treating TAC-induced heart failure in mice. The mechanism of ginsenoside Rg3 for improving heart and mitochondrial function in mice with heart failure was predicted through integrative analysis of the proteome and plasma metabolome. Glucose uptake and myocardial insulin sensitivity were evaluated using micro-positron emission tomography. The effect of ginsenoside Rg3 on myocardial insulin sensitivity was clarified by combining in vivo animal experiments and in vitro cell experiments. Results: Treatment of TAC-induced mouse models with ginsenoside Rg3 significantly improved heart function and protected mitochondrial structure and function. Fusion of metabolomics, proteomics, and targeted metabolomics data showed that Rg3 regulated the glycolysis process, and Rg3 not only regulated glucose uptake but also improve myocardial insulin resistance. The molecular mechanism of ginsenoside Rg3 regulation of glucose metabolism was determined by exploring the interaction pathways of AMPK, insulin resistance, and glucose metabolism. The effect of ginsenoside Rg3 on the promotion of glucose uptake in IR-H9c2 cells by AMPK activation was dependent on the insulin signaling pathway. Conclusions: Ginsenoside Rg3 modulates glucose metabolism and significantly ameliorates insulin resistance through activation of the AMPK pathway.

• BMB Reports
• /
• 제45권9호
• /
• pp.489-495
• /
• 2012

Ischemia is a blockage of blood supply due to an embolism or a hemorrhage in a blood vessel. When an organ cannot receive oxygenated blood and can therefore no longer replenish its blood supply due to ischemia, stresses, such as the disruption of blood glucose homeostasis, hypoglycemia and hypoxia, activate the AMPK complex. LKB1 and $CaMKK{\beta}$ are essential activators of the AMPK signaling pathway. AMPK triggers proangiogenic effects through the eNOS protein in tissues with ischemic conditions, where cells are vulnerable to apoptosis, autophagy and necrosis. The AMPK complex acts to restore blood glucose levels and ATP levels back to homeostasis. This review will discuss AMPK, as well as its key activators (LKB1 and $CaMKK{\beta}$), as a central energy regulator and evaluate the upstream and downstream regulating pathways of AMPK. We will also discuss how we can control this important enzyme in ischemic conditions to prevent harmful effects in patients with vascular damage.

• 약학회지
• /
• 제55권4호
• /
• pp.301-308
• /
• 2011

Diabetes has been one of major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has been focused as a novel therapeutic target for the treatment of metabolic syndromes, because AMPK increases glucose uptake through independent insulin signal pathway. In this study, we investigated the anti-diabetic effect of Angelica gigas Nakai extract (AGNEX), a mixture of decursin and decursinol angelate (53 : 47), decursin and decursinol angelate on blood glucose, glucose transport (GLUT) and AMPK expression levels in streptozotocin (STZ)-induced diabetic rats. To induce diabetes, 50 mg/kg of STZ was injected via i.v. route and AGNEX 2 mg/kg (STZ+AG), decursin 2 mg/kg (STZ+D), decursinol angelate 2 mg/kg (STZ+DA), and metformin 100 mg/kg (STZ+M) were administered orally for 21 days. STZ+DA group showed a significant decrease in fasting blood glucose levels compared to the other groups. Decursinol angelate significantly upregulated expression of glucose transporter 4 (GLUT4) and phosphorylation of AMPK (p-AMPK) in skeletal muscle of rats. In pancreas of rats, decursinol angelate significantly increased expression of GLUT2 through down-regulation of p-AMPK. In addition to the result of pancreatic islets morphology, AGNEX, decursin, decursinol angelate, and metformin treated group recovered ${\beta}$-cell damage by hyperglycemia. These results indicate that decursinol angelate might be a potential anti-diabetic agent and AGNEX could be useful in the treatment of diabetes mellitus.

• 생명과학회지
• /
• 제32권10호
• /
• pp.762-770
• /
• 2022

제 2형 당뇨병은 고혈당을 특징으로 하는 만성 대사성 질환으로 인슐린 민감성및 저항성을 개선하여 세포속으로 포도당 흡수를 촉진시킴으로서 완화될 수 있다. 본 연구는 triterpenoid 화합물인 betulinic acid가 3T3-L1 지방세포에서 인슐린 신호전달체계를 개선하여 포도당 흡수를 촉진시키는지를 조사하고 그 작용기전을 규명하였다. Betulinic acid는 3T3-L1 지방세포에서 농도의존적으로 포도당 흡수를 유의하게 증가시켰으며, 이는 PM-GLUT4의 발현 증가와 관련이 있음을 관찰하였다. Betulinic acid는 인슐린 신호전달 경로에서 PI3K의 활성화 및 IRS-1tyr, Akt의 인산화를 대조군에 비해 유의하게 증가시켰다. 또한 AMPK의 활성화를 나타내는 pAMPK와 AMPK 하위인자인 pACC의 수준을 유의하게 증가시켰다. Betulinic acid에 의한 PI3K 및 AMPK 경로의 활성화를 증명하기 위해, PI3K 억제제(Wortmannin)와 AMPK의 억제제(Compound C)를 사용하여 이들 처리에 의한 포도당 흡수능과 PM-GLUT4의 발현을 측정한 결과 이들의 발현이 유의하게 저해되었다. 본 연구에서 betulinic acid는 3T3-L1 지방세포에서 PI3K 및 AMPK 경로의 활성화를 통해 세포막으로 포도당 수송체인 GLUT4 전위를 촉진시키고 포도당 흡수를 증가시킬 수 있음을 나타내었다. 이러한 결과는 betulinic acid가 인슐린 민감성을 증진시키고 고혈당을 완화하는데 도움이 될 수 있음을 시사한다.

• 생명과학회지
• /
• 제31권1호
• /
• pp.1-9
• /
• 2021

본 연구는 갈조류 유래 물질인 후코이단이 인슐린 민감성을 증진시키는지를 규명하기 위하여 3T3-L1 지방세포에서 포도당 흡수에 미치는 후코이단의 영향을 측정하고 그 작용기전을 조사하였다. 후코이단은 지방세포에서 포도당 흡수를 유의하게 증가시켰으며 이는 PM-GLUT4의 발현 증가와 관련이 있음을 관찰하였다. 후코이단은 인슐린 신호전달 경로에서 PI3K의 활성화 및 pIRS1tyr, Akt, PKCλ/ζ의 인산화를 대조군에 비해 유의하게 증가시켰다. 또한, AMPK의 활성화를 나타내는 pAMPK 수준이 유의하게 증가하였다. 이들 PI3K 및 AMPK 활성화는 포도당 수송체인 GLUT4를 세포막으로 이동시켰으며 이로 인하여 PM-GLUT4의 발현이 증가되고 포도당 흡수가 촉진되었다. 후코이단에 의한 PI3K 및 AMPK 경로의 활성화를 증명하기 위해, PI3K 억제제인 Wortmannin과 AMPK의 억제제인 Compound C를 사용하여 이들 처리에 의한 포도당 흡수능과 PM-GLUT4의 발현을 측정한 결과 이들의 발현이 유의하게 저해되었다. 따라서 후코이단은 3T3-L1 지방세포에서 PI3K 및 AMPK 경로를 활성화시킴으로써 인슐린 민감성을 증진하고 포도당 흡수를 촉진시킬 수 있음을 나타내었다.

• 대한의용생체공학회:의공학회지
• /
• 제43권1호
• /
• pp.1-10
• /
• 2022

Non-alcoholic fatty liver disease(NAFLD) is excessive hepatic lipid accumulation mainly caused by obesity. This study aimed to evaluate whether micro-current stimulation(MCS) could modulate lipid metabolism regarding the Sirt1/AMPK pathway, fatty acid β-oxidation pathway, and lipolysis and lipogenesis-related factors in FL83B cells. For the NAFLD cell model, FL83B cells were treated with oleic acid for lipid accumulation. MCS were stimulated for 1 hr and used frequency 10 Hz, duty cycle 50%, and biphasic rectangular current pulse. The intensity of MCS was divided into 50, 100, 200, and 400 ㎂. Through the results of Oil red O staining, it was confirmed that MCSs with the intensity of 200 ㎂ and 400 ㎂ significantly reduced the degree of lipid droplet formation. Thus, these MCS intensities were applied to western blot analysis. Western blot analysis was performed to analyze the effects of MCS on lipid metabolism. MCS with the intensity of 400 ㎂ showed that significantly activated the Sirt1/AMPK pathway, a key pathway for regulating lipid metabolism in hepatocytes, and fatty acid β-oxidation-related transcription factors. Moreover, it activated the lipolysis pathway and suppressed lipogenesis-related transcription factors such as SREBP-1c, FAS, and PPARγ. In the case of MCS with the intensity of 200 ㎂, only PGC1α and SREBP-1c showed significant differences compared to cells treated only with oleic acid. Taken together, these results suggested that MCS with the intensity of 400 ㎂ could alleviate hepatic lipid accumulation by modulating lipid metabolism in hepatocytes.

• 생명과학회지
• /
• 제33권4호
• /
• pp.343-348
• /
• 2023

여드름은 가장 흔한 피부 질환 중 하나로 청소년기에 주로 발생한다. 호르몬, 유전, 환경적 요인이 알려져 있으며, 이 외에도 피부 과각화 및 C. acnes의 과증식 등이 여드름 발병에 중요한 역할을 한다. CBD는 통증과 스트레스 완화 및 항염증 특성을 갖는 것으로 알려져 있다. 뿐만 아니라, CBD가 함유된 대마 추출물이 여드름 완화 및 치료에 효과적인 소재로 보고되었다. 그러나 이에 대한 연구는 부족한 실정으로, 본 연구를 통하여 피지세포에서 CBD의 항여드름 활성을 확인하고자 하였다. 본 연구진은 세포에 CBD를 처리하여 지질 합성과 증식에 대한 억제 효과를 확인할 수 있었다. 그런 다음 CBD가 SREBP-1를 통해 지방 생성에 대한 억제 효과를 가지는 것을 입증했다. 또한 SREBP-1의 상위 조절자인 Akt와 AMPK가 CBD에 의해 조절되는 것을 확인했다. 종합하면, 본 연구 결과를 통해 CBD가 Akt/AMPK-SREBP-1 경로 조절을 통해 지방 생성을 억제하여 여드름 완화 소재로 이용될 수 있음을 시사하였다. 과각화증으로 인한 염증에 대한 CBD의 효과를 확인하기 위한 추가 연구가 필요하며, 이는 여드름에 대한 CBD의 활용 가능성을 높일 수 있을 것으로 사료된다.