• Title/Summary/Keyword: intracellular accumulation

검색결과 360건 처리시간 0.028초

Curcumin represses lipid accumulation through inhibiting ERK1/2-PPAR-γ signaling pathway and triggering apoptosis in porcine subcutaneous preadipocytes

  • Pan, Shifeng;Chen, Yongfang;Zhang, Lin;Liu, Zhuang;Xu, Xingyu;Xing, Hua
    • 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.

클로로필 제거 구기엽 추출물의 비알코올성 지방간 보호 효과 (Protective effect of chlorophyll-removed ethanol extract of Lycium barbarum leaves against non-alcoholic fatty liver disease)

  • 이한솔;배은영;김경아;이선영
    • Journal of Nutrition and Health
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    • 제56권2호
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    • pp.123-139
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    • 2023
  • 구기엽 추출물 (LLE)과 클로로필을 제거한 구기엽 추출물 (LLE(Ch-))이 MCD diet로 비알코올성 지방간을 유도한 C57BL/6 mouse와 팔미트산으로 지방 축적을 유도한 HepG2 세포에서 지방축적의 억제에 미치는 영향을 검토하였다. 대조군 대비 LLE(Ch-)는 혈장 TG 농도와 혈장 AST와 ALT의 활성을 유의하게 감소시켰으며 LLE군에서는 혈장 ALT 활성이 유의하게 감소하였다. 두 군 모두 간조직의 TG와 cholesterol 함량을 유의하게 낮추었으며 간조직의 병리학적 변화 결과에서 LLE군에 비해 LLE(Ch-)군에서 지방축적의 억제효과가 더 크게 나타났다. 팔미트산 0.5 mM을 처리한 HepG2 세포에서 LLE와 LLE(Ch-)가 1,000 ㎍/mL 농도까지 독성이 없었으며 대조군에 비하여 각각 200 ㎍/mL과 500 ㎍/mL 농도부터 세포 내 지방 축적량을 유의하게 감소시켰고 pAMPK와 pACC 발현이 농도 의존적으로 증가하였으며 FAS발현은 농도 의존적으로 억제되었다. 결과적으로 구기엽 100% 에탄올 추출물들은 간조직의 지방 축적을 억제할 수 있으며 그 효과는 클로로필 제거 구기엽의 활성이 좀 더 큰 것으로 나타났다. 따라서 이 두 소재 모두 항 지방간 효능이 있는 것으로 판단되며 기능성 소재로서의 개발 가능성을 확인하였다.

Anti-Oxidant and Anti-Adipogenic Effects of Ethanol Extracts from Wheat Germ and Wheat Germ Fermented with Aspergillus oryzae

  • Park, Euna;Kim, Hae Ok;Kim, Gyo-Nam;Song, Ji-Hye
    • Preventive Nutrition and Food Science
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    • 제20권1호
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    • pp.29-37
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    • 2015
  • Most of the wheat germ in cereal grains is removed during the milling process. Various physiological effects have been reported for bioactive substances in wheat germ such as phenolic acids and flavonoids. In this study, the antioxidant and anti-adipogenic effects of ethanol extracts from wheat germ (WGE) and wheat germ fermented with Aspergillus oryzae (F-WGE) were investigated in HepG2 and 3T3-L1 cells. The anti-oxidant activity of F-WGE was demonstrated by a dose-dependent increase in the enhanced scavenging capacity of hydroxyl radicals and $Cu^{2+}$-chelating activity compared to WGE. WGE and F-WGE treatment at doses between 10 and $400{\mu}g/mL$ did not affect the viability of HepG2 and 3T3-L1 cells. Intracellular ROS levels from $Cu^{2+}$-induced oxidative stress were significantly decreased by F-WGE treatment in HepG2 cells compared to WGE. Lipid accumulation was increased in 3T3-L1 adipocytes by $100{\mu}M$ $Fe^{2+}$ treatment, but the accumulation was strongly inhibited by $100{\mu}g/mL$ of WGE and F-WGE treatment. These results suggest that changes in bioactive substances during the fermentation of wheat germ can potentiate scavenging activities against transition metal-induced oxidative stress and lipid accumulation in 3T3-L1 adipocytes. Therefore, we propose that F-WGE is a novel food materials and provided scientific evidences for its efficacy in the development of functional foods.

북방전복(Haliotis discus hannai) 난모세포의 미세구조적 분화 (Microstructural Differentiation of the Oocyte in the Abalone Haliotis discus hannai)

  • 김혜진;김현진;김영숙;이정식
    • 한국수산과학회지
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    • 제53권1호
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    • pp.90-97
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    • 2020
  • The purpose of this study was to provide basic information on sexual maturity and reproductive biology for the management of biological resources in abalone Haliotis discus hannai. The nucleus of the oogonium occupied about 42% of the cytoplasm, and had a distinctive basophilic chromatin. The cytoplasm of previtellogenic oocytes was homogeneous and the size of nuclear pores increased. Fine granular and vacuolar yolk granules were observed in the cytoplasm of the initial vitellogenic oocyte. In this stage, the egg stalk and jelly membrane began to develop. The nucleus of the active vitellogenic oocyte was located near the animal pole. Yolk granules were strongly acidophilic. Lampbrush chromosomes were observed in the nucleus and rough endoplasmic reticulum. Annulate lamellae developed in the cytoplasm. The shape of the ripe oocyte was rounded polygonal. The size of ripe oocytes was 202.9±21.40×142.1±18.82 ㎛ and the thickness of the jelly membrane was 10.1±1.52 ㎛. These results show that yolk accumulation in H. discus hannai is based on two methods: exogenous accumulation, through the egg stalk, and endogenous accumulation, through intracellular organelles. Management of biological resources will be necessary when oocytes predominate after the active vitellogenic stage.

분리 위선세포에서 가역성 프로톤 펌프 억제제 YH1238 및 YH1885의 위산분비 억제효과 (Inhibitory Effects of Reversible Proton Pump Inhibitors YH 1238 and YH1885 on Acid Secretion in Isolated Gastric Cells)

  • 김혜영;김동구;이봉용;이종욱;김경환
    • The Korean Journal of Physiology and Pharmacology
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    • 제1권3호
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    • pp.337-343
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    • 1997
  • Antiulcer effects of YH1238 and YH1885 were determined in the isolated gastric cells from human and rabbit stomach. Intracellular accumulation of $[^{14}C]-aminopyrine\;and\;[^{14}C]-glucose$ oxidation were used as indicators of acid secretory ability of the gastric cells. Unstimulated and stimulated gastric cells with dibutyryl cAMP$(10^{-3}M)$ were used and the inhibitory effects of YH1238 and VH1885 on acid secretion were compared with known proton pump inhibitors such as omerrazole and SK&F 96067. Dibutyryl cAMP stimulated the $[^{14}C]-aminopyrine$ accumulation and $[^{14}C]-glucose$ oxidation, which were inhibited by YH1238, YH1885, SK&F 96067 and omeprazole. Inhibitory effects of YH1238, YH1885 and omeprazole on $[^{14}C]-aminopyrine$ accumulation in stimulated gastric cells were more potent than that of SK&F 96067 at the concentration of $10^{-5}M$. It is suggested that the reversible proton pump inhibitors YH1238 and YH1885 would be effective antiulcer agents.

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Ginseng seed oil ameliorates hepatic lipid accumulation in vitro and in vivo

  • Kim, Go Woon;Jo, Hee Kyung;Chung, Sung Hyun
    • Journal of Ginseng Research
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    • 제42권4호
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    • pp.419-428
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    • 2018
  • Background: Despite the large number of studies on ginseng, pharmacological activities of ginseng seed oil (GSO) have not been established. GSO is rich in unsaturated fatty acids, mostly oleic and linoleic acids. Unsaturated fatty acids are known to exert a therapeutic effect in nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the protective effect and underlying mechanisms of GSO against NAFLD using in vitro and in vivo models. Methods: In vitro lipid accumulation was induced by free fatty acid mixture in HepG2 cells and by 3 wk of high fat diet (HFD)-feeding in Sprague-Dawley rats prior to hepatocyte isolation. The effects of GSO against diet-induced hepatic steatosis were further examined in C57BL/6J mice fed a HFD for 12 wk. Results: Oil Red O staining and intracellular triglyceride levels showed marked accumulation of lipid droplets in both HepG2 cells and rat hepatocytes, and these were attenuated by GSO treatment. In HFD-fed mice, GSO improved HFD-induced dyslipidemia and hepatic insulin resistance. Increased hepatic lipid contents were observed in HFD-fed mice and it was lowered in GSO (500 mg/kg)-treated mice by 26.4% which was evident in histological analysis. Pathway analysis of hepatic global gene expression indicated that GSO increased the expression of genes associated with ${\beta}$-oxidation (Ppara, Ppargc1a, Sirt1, and Cpt1a) and decreased the expression of lipogenic genes (Srebf1 and Mlxipl), and these were confirmed with reverse transcription and quantitative polymerase-chain reaction. Conclusion: These findings suggest that GSO has a beneficial effect on NAFLD through the suppression of lipogenesis and stimulation of fatty acid degradation pathway.

Paeonia anomala L.의 물 추출물이 3T3-L1 지방 전구세포의 분화 및 지방 축적에 미치는 영향 (Paeonia anomala L. water extract attenuates differentiation and fat accumulation in 3T3-L1 preadipocytes)

  • 최문열;김미형;김미려
    • 대한본초학회지
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    • 제39권2호
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    • pp.27-33
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    • 2024
  • Objective : Obesity is a disease caused by energy imbalance and increases the risk of complications such as cardiovascular disease and cancer. Additionally, a recent study reported that excessive production of ROS stimulates the expression of transcription factors related to adipogenesis, such as PPAR-𝛾, C/EBP-𝛼 and 𝛽, in 3T3-L1 cells. In this study, Paeonia anomala L. (PAL) was selected as a candidate for improving and preventing obesity from Mongolian medical literature, and its effect on fat metabolism was observed in vitro. Methods : The activity of PAL extract against lipid accumulation was measured in 3T3-L1 cells through Oil red O staining. Additionally, the expression of lipid metabolism-related proteins was measured by western blot. Results : Intracellular lipid accumulation was significantly lower in the treatment group than in the control group. In addition, pAMPK/AMPK protein expression in the treatment group tended to increase in a concentration-dependent manner, and PPAR-𝛾 protein expression in the treatment group showed a significant decrease in a concentration-dependent manner compared to the control group. Conclusion : These results suggest that PAL extract may have an anti-obesity effect, and it is believed that it can be used to develop functional materials for the treatment of obesity.

홍삼 사포닌 분획의 Nrf2 Keap1 신호전달체계 조절을 통한 지방축적 및 활성산소종 억제효과 (Red ginseng-derived saponin fraction inhibits lipid accumulation and reactive oxygen species production by activating nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) pathway)

  • 김채영;강보빈;황지수;최현선
    • 한국식품과학회지
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    • 제50권6호
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    • pp.688-696
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    • 2018
  • 본 연구에서는 홍삼 사포닌 분획(SF)으로부터 진세노사이드의 조성을 분석하고 지방세포의 분화 및 지방축적에 대한 효과를 측정하였다. SF는 지방분화인자인 $PPAR{\gamma}$, $C/EBP{\alpha}$의 단백질 양을 억제함으로써 지방분화 동안 효과적으로 지방축적을 억제하였으며 주로 지방분화 초기시점부터 지방분화 초기인자인 $C/EBP{\beta}$, KLF2의 조절작용을 통해 지방축적을 억제하는 것으로 관찰되었다. SF는 또한 지방분화 동안 생성되는 ROS의 생성을 효과적으로 억제하였는데 이는 SF가 산화방지 시스템인 Nrf2/Keap1 경로를 활성화하기 때문으로 판단되며 특히 Nrf2의 핵 내로의 진입을 활성화 함으로써 Nrf2의 타겟 산화방지 분자들인 HO-1, NQO1의 발현을 촉진하였다. 이는 지방분화 동안 SF의 지방축적 억제 효과가 Nrf2의 활성화와 밀접하게 관련이 있음을 보여준다.

Anti-Inflammatory Effects of Water Chestnut Extract on Cytokine Responses via Nuclear Factor-κB-signaling Pathway

  • Kim, Bora;Kim, Jin Eun;Choi, Byung-Kook;Kim, Hyun-Soo
    • Biomolecules & Therapeutics
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    • 제23권1호
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    • pp.90-97
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    • 2015
  • Water chestnut (Trapa japonica Flerov.) is an annual aquatic plant. In the present study, we showed that the treatment of water chestnut extracted with boiling water resulted in a significant increase 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and decrease the intracellular $H_2O_2$-induced accumulation of reactive oxygen species. In addition, water chestnut extract (WCE) inhibited lipopolysaccharide (LPS)-induced nitric oxide production and suppressed mRNA and protein expression of the inducible nitric oxide synthase gene. The cytokine array results showed that WCE inhibited inflammatory cytokine secretion. Also, WCE reduced tumor necrosis factor-${\alpha}$- and interleukin-6-induced nuclear factor-${\kappa}B$ activity. Furthermore, during sodium lauryl sulfate (SLS)-induced irritation of human skin, WCE reduced SLS-induced skin erythema and improved barrier regeneration. These results indicate that WCE may be a promising topical anti-inflammatory agent.

Quantitative and qualitative analysis of autophagy flux using imaging

  • Kim, Suree;Choi, Soohee;Kang, Dongmin
    • BMB Reports
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    • 제53권5호
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    • pp.241-247
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    • 2020
  • As an intracellular degradation system, autophagy is an essential and defensive cellular program required for cell survival and cellular metabolic homeostasis in response to various stresses, such as nutrient deprivation and the accumulation of damaged organelles. In general, autophagy flux consists of four steps: (1) initiation (formation of phagophore), (2) maturation and completion of autophagosome, (3) fusion of autophagosomes with lysosomes (formation of autolysosome), and (4) degradation of intravesicular components within autolysosomes. The number of genes and reagents that modulate autophagy is increasing. Investigation of their effect on autophagy flux is critical to understanding the roles of autophagy in many physiological and pathological processes. In this review, we summarize and discuss ways to analyze autophagy flux quantitatively and qualitatively with the use of imaging tools. The suggested imaging method can help estimate whether each modulator is an inhibitor or a promoter of autophagy and elucidate the mode of action of specific genes and reagents on autophagy processes.