• 디지털융복합연구
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• 제17권8호
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• pp.283-291
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• 2019

간성 지방생성과 지방 대사에 있어서 FABP5의 역할에 대하여 알아보고자 하였다. 마우스에 바이러스 입자를 이용하여 간에서 FABP5를 과발현 그리고 침묵시켜 이용하였다. 마우스에 서양식 또는 일반 사료를 1주일간 섭취시키고 24시간 동안 금식한 후 희생하였다. 간을 기계적으로 분쇄하여 웨스턴 블?으로 단백질 농도를 측정하였고, mRANA 분석에는 RT-PCR을 이용하였다. 간과 혈청의 지질 분석에는 박층 크로마토그래피를 이용하였다. 서양식이나 고농도 포화 지방식을 급식한 쥐에서 FABP5 발현이 높은 증가를 보였으나, FABP5 mRNA 발현은 급식에 비해 단식조건에서 급격히 감소하였다. FABP5를 과발현 시킨 상태에서 급식과 금식을 실시한 결과 간성 TG가 중요하게 증가하였다. 간성 유리 콜레스테롤은 급식상태에서 현저히 감소하였다. FABP5 발현 억제 시 간성 TG가 상당히 감소하였다. 결과들에서 보듯이, FABP5가 간지질 생성에 중요한 역할을 하며, 정상 상태 및 탄수화물 유도 조건에서 간성 TG 저장형성에 관여할 것으로 사료된다. FABP5는 비알코올성 지방간 질환, 대사증후군, 비만 치료에 활용될 수 있을 것으로 사료된다. 더 나아가, FABP5 발현에 어떤 전사인자가 관여하는지에 대한 연구가 필요하다.

• Journal of Nutrition and Health
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• 제54권5호
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• pp.448-458
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• 2021

본 연구는 뽕나무 열매 착즙 분말 (MJ)이 지방세포 분화과정에서 염증에 관여하는 유전자 발현 및 miR-132/143 조절에 미치는 효과에 중점을 두고 조사하였다. MJ는 3T3-L1 지방세포 분화 동안 지질축적이 억제되었고 PPAR-γ, CEBP-α 및 aP2와 같은 지방형성 유전자 발현을 억제하였다. 또한 염증 조절 매개체인 TNF-α, IL-6, MCP-1 및 iNOS 유전자 발현이 MJ 처리에 의해 감소되었다. MJ의 지질 축적 억제 효과는 염증과 지방분화에 관여하는 miR-132/143의 발현 감소와 관련이 있음을 확인하였다. 따라서 MJ는 염증을 동반하는 비만 예방 및 치료에 도움이 될 수 있는 식품 소재로서 가능성이 있음을 시사하고 있다. 그러나 MJ의 주요 성분인 안토시아닌의 생체이용율은 1-2% 미만으로 추정되며 예상되는 표적 조직이나 혈류에서 미량 검출되는 것으로 알려져 있다 [33]. 이를 해결하기 위해서는 생체 내 동물실험을 통한 다각적인 분석이 향후 진행되어야 할 것으로 판단된다.

• Animal Bioscience
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• 제35권5호
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• pp.763-777
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• 2022

Objective: Excessive lipid accumulation in adipocytes results in prevalence of obesity and metabolic syndrome. Curcumin (CUR), a naturally phenolic active ingredient, has been shown to have lipid-lowering effects. However, its underlying mechanisms have remained largely unknown. Therefore, the study aims to determine the effect of CUR on cellular lipid accumulation in porcine subcutaneous preadipocytes (PSPA) and to clarify novel mechanisms. Methods: The PSPA were cultured and treated with or without CUR. Both cell counting Kit-8 and lactate dehydrogenase release assays were used to examine cytotoxicity. Intracellular lipid contents were measured by oil-red-o staining extraction and triglyceride quantification. Apoptosis was determined by flow cytometry and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labelling assay. Adipogenic and apoptosis genes were analyzed by quantitative polymerase chain reaction and Western blot. Results: The CUR dose-dependently reduced the proliferation and lipid accumulation of PSPA. Noncytotoxic doses of CUR (10 to 20 μM) significantly inhibited extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and expression of adipogenic genes peroxisome proliferation-activity receptor-γ (PPAR-γ), CCAAT/enhancer binding protein-α, sterol regulatory element-binding protein-1c, adipocyte protein-2, glucose transporter-4 as well as key lipogenic enzymes fatty acid synthase and acetyl-CoA carboxylase, while ERK1/2 activation significantly reversed CUR-reduced lipid accumulation by increasing PPAR-γ. Furthermore, compared with differentiation induced media treated cells, higher dose of CUR (30 μM) significantly decreased the expression of AKT and B-cell lymphoma-2 (BCL-2), while increased the expression of BCL-2-associated X (BAX) and the BAX/BCL-2 expression ratio, suggesting triggered apoptosis by inactivating AKT and increasing BAX/BCL-2 ratio and Caspase-3 expression. Moreover, AKT activation significantly rescued CUR inhibiting lipid accumulation via repressing apoptosis. Conclusion: These results demonstrate that CUR is capable of suppressing differentiation by inhibiting ERK1/2-PPAR-γ signaling pathway and triggering apoptosis via decreasing AKT and subsequently increasing BAX/BCL-2 ratio and Caspase-3, suggesting that CUR provides an important method for the reduction of porcine body fat, as well as the prevention and treatment of human obesity.

• 대한본초학회지
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• 제34권6호
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• pp.79-89
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• 2019

Objective : This study investigated the anti-diabetic effects of DM1, a herbal mixture with Atractylodis Rhizoma, Anemarrhenae Rhizoma, and Cinnamomi Cortex in high fat diet (HFD)-induced diabetic mice and the mechanism in C2C12 mouse skeletal muscle cells. Methods : The C57B/6 mice were fed high fat for 12 weeks, and then administrated DM1 extract (500 mg/kg, p.o.) for 4 weeks. The changes of body weight, calorie and water intakes, fasting blood glucose levels and the serum levels of glucose, insulin, triglyceride, HDL-cholesterol, AST and ALT were measured in mice. The histological changes of liver and pancreas tissues were also observed by H&E stain. C2C12 myoblasts were differentiated into myotubes and then treated with DM1 extract (0.5, 1, and 2 mg/㎖) for 24 hr. The expression of myosin heavy chain (MHC), PGC1α, Sirt1 and NRF1, and the AMPK phosphorylation were determined in the myotubes by western blot, respectively. Results : The DM1 extract administration significantly decreased the calorie and water intakes, glucose, triglyceride, AST and ALT levels and increased insulin and HDL-cholesterol in HFD-induced diabetic mice. DM1 extract inhibited lipid accumulation in liver tissue and improved glucose tolerance. In C2C12 myotubes, DM1 treatment increased the expression of MHC, PGC1α, Sirt-1, NRF-1 and the AMPK phosphorylation. Conclusion : In our results indicate that DM1 can improve diabetic symptoms by decreasing the obesity, glucose tolerance and fatty liver in HFD-induced diabetic mice, and responsible mechanism is might be related with energy enhancement.

• 대한본초학회지
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• 제39권3호
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• pp.57-67
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• 2024

Objectives : The aim of this study is to evaluate the potential biological activity of Veronica incana extracts (VIE) through in vitro, ex vivo, and in vivo experiments. Methods : In vitro, we conducted analyses on the total polyphenol (TP) and total flavonoid (TF) levels, alongside DPPHand ABTS radical scavenging activities. Ex vivo evaluations on adipose tissue measured glycerol release as a marker of lipolysis. In LPS-induced RAW 264.7 cells, we quantified nitric oxide (NO) production. Following H₂O₂ induction in U2OS cells, we performed mitochondrial assays such as MitoSox and MitoTracker. Moreover, Bodipy assays were conducted in 3T3-L1 cells. In vivo, we performed anti-osteoarthritis effect of VIE against monosodium iodoacetate (MIA)-induced osteoarthritis in rats. Results : The results presented encompass a myriad of models, from cell culture to animal experiments as well as ex vivo studies. VIE demonstrated high TP and TF contents, potent DPPH and ABTS scavenging activities, and regulated glycerol release. Moreover, the inhibition of NO production in LPS-induced inflammation was notably confirmed and the reduction of lipid droplets was distinctly shown. Furthermore, in H₂O₂-induced U2OS cells, MitoSox was effectively reduced while MitoTracker noticeably increased. In vivo assays confirmed a significant increase in hindpaw weight distribution (HWD) decreased by MIA after VIE treatment. Additionally, VIE inhibited serum inflammatory cytokines (TNF-𝛼, IL-6, and IL-1𝛽) and MDA levels in joint tissue. Conclusion : In conclusion, Veronica incana exhibited various pharmacological effects including antioxidant, anti-obesity, and anti-inflammatory properties.

• 한방비만학회지
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• 제23권2호
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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.

• 한국식품영양과학회지
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• 제45권5호
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• pp.664-670
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• 2016

Polyglutamic acid(PGA) 함유량이 증대된 청국장이 조골세포에 미치는 영향을 세포 수준에서 관찰하고자 하였다. 조골세포에 미치는 영향을 관찰하기 위하여 세포 생존율, 염기성 인산분해효소(alkaline phosphatase, ALP) 활성, 골 석회화 형성능, 조골세포 분화 관련 유전자 발현능을 측정하였다. 세포 독성이 없는 농도에서 염기성 인산분해효소 활성을 측정한 결과 농도에 의존적으로 ALP 활성이 증가하였으며, 일반 청국장 A보다 PGA 함유량이 증가한 청국장 B가 더 높은 ALP 활성 증가 효과를 나타내었다. 청국장의 골 석회화 형성능을 측정한 결과 역시 청국장 A보다 B가 더 높은 석회화 형성능을 나타내었다. 또한 분화 관련 유전자인 OCN, OPN, Col1, ALP 역시 청국장 B가 A보다 유전자 발현이 더 높게 나타났다. 이러한 실험 결과를 바탕으로 PGA가 증대된 청국장이 기존 청국장보다 조골세포의 활성에 효과적일 것으로 생각한다.

• 생명과학회지
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• 제24권11호
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• pp.1244-1251
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• 2014

길경(桔梗, Platycodon grandiflorum)은 도라지의 뿌리로 항염증, 항알러지, 면역 반응, 당뇨, 고지혈증 및 항암 효과 등을 가지고 있는 것으로 알려져 있다. 하지만 길경의 항암 효과에 대한 연구는 미미하며, 길경이 유발하는 autophagy에 대한 연구는 되어 있지 않다. 본 연구에서는 HCT-116 대장암 세포주에서 길경 추출물이 autophagy와 apoptosis를 유발하면서 세포 성장을 억제하는지의 여부를 조사하였다. 길경 추출물은 농도 및 시간의존적으로 세포의 증식을 억제하였으며, 길경 추출물에 의해 나타나는 apoptosis는 caspase의 활성이 부분적으로 관여되어 있음을 알 수 있었다. 또한, 길경 추출물의 처리는 autophagy에 의해 나타나는 공포를 형성하면서 autophagy와 관련되어 있는 여러 단백질의 발현 조절 및 LC3 단백질의 축적이 동반되었다. 길경 추출물에 의해 유도되는 autophay와 apoptosis의 관계를 알아보기 위해서 3-MA나 bafilomycin A1을 처리하여 autophagy를 억제하였을 때 apoptosis가 유의적으로 증가됨을 알 수 있었다. 흥미롭게도 bafilomycin A1을 처리한 결과에서 길경 추출물에 의한 세포성장 억제가 뚜렷하게 회복되는 양상을 보였다. 따라서 본 연구의 결과는 HCT-116 세포에서 길경 추출물에 의해 유도된 autophagy는 세포 보호적인 작용이 아닌 autophagic cell death이며, 길경 추출물이 대장암 세포주에서 암세포의 사멸을 유도하는 효과적인 대안이 될 수 있음을 알 수 있었다.

• Journal of Microbiology and Biotechnology
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• 제25권12호
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• pp.2146-2152
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• 2015

Apios americana Medik (hereinafter Apios) has been reported to treat diseases, including cancer, hypertension, obesity, and diabetes. The therapeutic effect of Apios is likely to be associated with its anti-inflammatory activity. This study was conducted to evaluate the protective effects of Apios in animal models of acute lung injury induced by lipopolysaccharide (LPS) or pandemic H1N1 2009 influenza A virus (H1N1). Mice were exposed to LPS or H1N1 for 2-4 days to induce acute lung injury. The treatment groups were administered Apios extracts via oral injection for 8 weeks before LPS treatment or H1N1 infection. To investigate the effects of Apios, we assessed the mice for in vivo effects of Apios on immune cell infiltration and the level of pro-inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid, and histopathological changes in the lung. After induction of acute lung injury, the numbers of neutrophils and total cells were lower in the Apios-treated groups than in the non-Apios-treated LPS and H1N1 groups. The Apios groups tended to have lower levels of tumor necrosis factor-a and interleukin-6 in BAL fluid. In addition, the histopathological changes in the lungs were markedly reduced in the Apios-treated groups. These data suggest that Apios treatment reduces LPS- and H1N1-induced lung inflammation. These protective effects of Apios suggest that it may have therapeutic potential in acute lung injury.

• Clinical and Experimental Pediatrics
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• 제56권4호
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• pp.151-158
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• 2013

Purpose: We investigated the mRNA levels of peroxisome proliferator-activated receptor (PPAR)-${\alpha}$, PPAR-${\gamma}$, adipokines, and cytokines in the lung tissue of lean and obese mice with and without ovalbumin (OVA) challenge, and the effect of rosiglitazone, a PPAR-${\gamma}$ agonist. Methods: We developed 6 mice models: OVA-challenged lean mice with and without rosiglitazone; obese mice with and without rosiglitazone; and OVA-challenged obese mice with and without rosiglitazone. We performed real-time polymerase chain reaction for leptin, leptin receptor, adiponectin, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-${\alpha}$, transforming growth factor (TGF)-${\beta}$, PPAR-${\alpha}$ and PPAR-${\gamma}$ from the lung tissue and determined the cell counts and cytokine levels in the bronchoalveolar lavage fluid. Results: Mice with OVA challenge showed airway hyperresponsiveness. The lung mRNA levels of PPAR${\alpha}$ and PPAR-${\gamma}$ increased significantly in obese mice with OVA challenge compared to that in other types of mice and decreased after rosiglitazone administeration. Leptin and leptin receptor expression increased in obese mice with and without OVA challenge and decreased following rosiglitazone treatment. Adiponectin mRNA level increased in lean mice with OVA challenge. Lung VEGF, TNF-${\alpha}$, and TGF-${\beta}$ mRNA levels increased in obese mice with and without OVA challenge compared to that in the control mice. However, rosiglitazone reduced only TGF-${\beta}$ expression in obese mice, and even augmented VEGF expression in all types of mice. Rosiglitazone treatment did not reduce airway responsiveness, but increased neutrophils and macrophages in the bronchoalveolar lavage fluid. Conclusion: PPAR-${\alpha}$ and PPAR-${\gamma}$ expressions were upregulated in the lung tissue of OVA-challenged obese mice however, rosiglitazone treatment did not downregulate airway inflammation in these mice.